Oncology

nurse holding the hand of an older man

Winning the Biosimilar Race: Trastuzumab Biosimilar Phase III Breast Cancer Study

At a Glance

A sponsor of a global Phase 3 study of a trastuzumab biosimilar came to PSI after falling behind schedule with their current CRO. Drawing on PSI’s biosimilar experience going back to the first such product ever approved by the FDA, we supported the sponsor in recruiting the required 800 patients in just over a year, leading to an EMA approval. Before getting there, though, we had to navigate additional challenges, including an unexpected delay that led to late site activation – just before the summer slow-down.

enrollment graph with red and blue lines

Phase 3 study in a Trastuzumab biosimilar

Sponsor Challenges

Speed and cost are key for biosimilar development, but development is not necessarily less complex than for a reference biologic. It requires state-of-the-art manufacturing expertise to ensure the biosimilar is “highly similar” with no significant clinical differences in safety profile, efficacy, and potency. Competition for patients against other studies with novel therapeutics often amplifies these challenges.

For PSI’s transition of a global Phase 3 study of a trastuzumab biosimilar in HER2+ early breast cancer patients, it was critical to understand the patient flow from surgery to chemotherapy and back. An additional challenge was that the sponsor’s previous CRO had placed the study primarily in Western countries, where higher standards of care and availability of trastuzumab are common.

How our team made a difference

1) Understanding the landscape

PSI started by thoroughly assessing the country landscape and the product’s reception by sites from our vast oncology network. We selected 100 sites in 10 countries in Eastern Europe, Asia-Pacific, Latin America, and South Africa. The US was also included due to prior expectations from the FDA. The data from other countries was perfectly acceptable.

2) Ready for the green light

Our startup roadmap had to be adjusted when the sponsor put the study on hold for internal reasons, leading to almost half a year of delay in site activation. While waiting for the go-ahead to resume activation, the PSI team prepared contracts ahead of time and had vendors and sites in standby mode. The preparation paid off: as soon as PSI was notified, our teams activated the remaining sites almost simultaneously.

3) Relentless focus on patient enrollment

Because of the delay, site activation occurred just before the summer break, leading to a slow start to patient enrollment. PSI and the sponsor decided to implement several enrollment-boosting measures and organized local investigator meetings for open discussion. A common concern we heard from sites was time and resources, so we optimized site processes to make their work more efficient and focused on the personal relationships of our CRAs and Medical Monitors with investigators and site staff. By optimizing our SDV strategy, close cost control, and the implementation of a blinding system that allowed us to perform drug accountability without the need for a whole unblinded team, we obtained important cost efficiencies.

Program Successes and Outcomes

  • 800 patients enrolled in just over a year
  • Last patient enrolled only 2 months later than initial goal, despite 6-month startup delay
  • Successful FDA inspection and EMA approval

Learn how PSI can support your hemophilia study at the resources below or contact us today

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral. 

Oncology Experience

Breast Cancer, Lung Cancer, Prostate Cancer, Colorectal Cancer, Ovarian Cancer, and other Oncology indications. 93 percent of PSI’s oncology studies meet or beat projected enrollment timelines.

The Future of Oncology Clinical Research

This white paper provides essential insights for sponsors into the trends with the greatest potential to affect clinical trial design and operationalization.

Winning the Biosimilar Race: Trastuzumab Biosimilar Phase III Breast Cancer Study Read More »

Case Study: How VISIONAL™ is Helping to Accurately Predict Study Enrollment Timelines

At a Glance: AI and ML-powered insights for your next trial

A sponsor of a challenging breast cancer study needed to identify the optimal mix of countries and sites with similar experience and access to a hard-to-recruit subpopulation of breast cancer. Using internal and external data sources, PSI’s VISIONAL™ platform compared thousands of feasible country-site combinations and recommended the optimal enrollment scenario to meet the sponsor’s timelines and cost constraints.

Trial Enrollment Recommendations from VISIONAL™
key metrics for VISIONAL case study. 520 patients with heart in hand symbol. 126 trial sites with a target in a human head symbol. 7 countries with a world symbol. all in white text.

Sponsor Challenges

The study targeted patients pretreated with recently approved drugs. Our key criteria for country and site selection included local standards of care, historical performance in the indication, and current competition. After the initial planning had begun, the sponsor also requested 20% of patients from Latin America.

How VISIONAL™ Helps Make Strategic Decisions

Working with internal and external data sources and KOLs, PSI feasibility team quickly pulled all available data on standards of care, site performance, and historical enrollment rates, carefully curated for similarity. The dataset included 40+ countries in North America, South America, Europe, Asia-Pacific, and Africa. Using this trove of data, VISIONAL™ compared hundreds of country/site combinations, taking into account study costs and probability of success.

We were able to easily adjust the constraints for regional patient quotas as well as additional requirements from the FDA and EMA after two rounds of protocol review.

Results

1. Optimal Enrollment Scenario

VISIONAL™ recommended the most optimal combination of sites, countries, and timelines based on the current landscape and historical benchmarks, while taking into account all constraints set by the sponsor and the FDA.

2. Cost vs. Speed
The system recommended the fastest and most cost-efficient scenario within the sponsor’s budget range and timelines. We were also able to quickly evaluate alternative options:

  • Faster scenarios with an acceptable risk level
  • Longer but less expensive scenarios
  • Scenarios that buffer for unexpected delays

3. Customizable and Adaptive Reports
The initial work done during the planning stage also provided the sponsor with peace of mind during the study launch with the ability to rapidly model new scenarios based on additional constraints/new requirements.

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral. 

Therapeutic Areas

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Case Study: How VISIONAL™ is Helping to Accurately Predict Study Enrollment Timelines Read More »

up close image of a small clear vial, a CT scan of a brain and a stethoscope

Case Study: Phase 3 Radiopharmaceutical Clinical Trial in Oncology

At a Glance: FDA Approval in 4 Years

Radiopharmaceutical clinical trials face a host of logistical challenges from startup through the clinical phase. A sponsor of a pivotal Phase 3 prostate cancer study investigating a radiopharm product approached PSI for support based on our experience and established network of over 400 global radiopharmaceutical sites. By working closely with our sites and vendors, PSI met or beat all critical milestones, helping our client secure FDA approval for their radiopharmaceutical product in under four years.

graph representing predicted vs. actual patient enrollment and patient screening numbers
Patient Screening and Enrollment Numbers
key metrics for radiopharmacy case study. 1200 patients with heart in hand symbol. 860 trial sites with a target in a human head symbol. 10 countries with a world symbol. 90 trial sites with a hospital symbol. all in white text.

Sponsor Challenges

The major challenges in global nuclear medicine trials include the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. The investigational product in this study had a half-life of three days, necessitating diligent time management and site engagement to deliver the study on schedule.

PSI Strategy

To make sure eligible patients didn’t miss these three-day windows, PSI’s CRAs encouraged sites to maintain frequently updated pre-screening logs and regularly discuss the pool of potential patients with the investigators. We also worked closely with sites and the manufacturing facilities to time the inclusion of each patient appropriately, especially around local bank holidays when a manufacturing facility would not be available.

Results

1) Expedited Study Timelines
PSI met or beat all critical milestones during the study, including achieving FPI in the US in less than 3 months and completing NDA submission one month ahead of schedule.

2) 99% Enrolling Sites
Only one out of all initiated sites did not enroll a patient.

3) Successful Regulatory Approval
After passing three FDA inspections without major findings, PSI’s regulatory experts helped our client secure FDA approval in under four years.

“I would personally like to acknowledge and thank the entire PSI team and leadership for the dedication, perseverance and determined support that supported the early completion of the study. Your team have showcased all the capabilities and attributes of a best-in-class CRO for project delivery.”
abstract background purple cells
--Global Head
External Relationship Management

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral. 

Therapeutic Areas

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Case Study: Phase 3 Radiopharmaceutical Clinical Trial in Oncology Read More »

red blood cells under a microscope viewing with a purple dye contrast

Case Study: Optimizing Feasibility and Start-Up for a Phase III HemOnc Clinical Trial

At a Glance

No trial is ever easy. But with the continued effects of the global pandemic and the war in Ukraine, the sponsor had larger than average challenges. Nonetheless, PSI managed to demonstrate swift feasibility and start-up ahead of schedule, leveraging site relationships, and fostering team consistency and stability. In the end the study completed enrollment of nearly 900 patients on time at as many as 370 sites all around the world. Italy and Australia showed up as the top enrolling countries.
graph depicting planned vs. actual patient enrollment for the hemonc case study. There is a red and blue line
Patient Enrollment Numbers
Key metrics for HemOnc case study 900 patients enrolled with heart in hand symbol. 425 sites activated with target in a persons head symbol. 30 countries with a world symbol.

Sponsor Challenges

Enrolling over 900 patients and in a clinical trial of this complexity would pose a challenge even in the most mundane of years. Add to that continual pandemic consequences and a global conflict, the stage is set for every possible delay and communication breakdown. The sponsor needed a CRO willing to tackle an aggressive recruitment plan and provide a solid partnership in order for the trial to succeed.

Start-Up in Sync

Staying on time means starting on time. Working closely with sites to understand how the pandemic affected their ability to meet site activation, PSI offered them several technical options that allowed for remote site selection visits. PSI managed to identify over 3000 sites and select about 500 sites 3 months ahead of schedule.

Additionally, feasibility projections were actually reflected in enrollment, not merely a best-case scenario or wishful thinking. This is due in large part to knowing the sites. Today, PSI would have also added machine-learning-powered tool, VISIONAL™, to generate the most optimal enrollment scenarios that could potentially further reduce the study time and cost.

Racalibrating the Geo-mix

Not every CRO can offer flexibility and adaptability, especially in a short amount of time. During enrollment, a change of strategy on the sponsor side called for more sites, and swiftly. In order to do this, countries with initially smaller projected sites and patients had to ramp up with little to no interruption. The only way this could be accomplished was with previously established solid global site relationships and coordination and stellar communication on every level of the study team.

Managing Motivation, Staffing, & Velocity

To motivate teams on a country level, PSI staff focused on maintaining a sense of competition between teams. This helped create a friendly sense of excitement as countries saw their recruitment numbers grow.

Continuity of the study team also played an enormous role in the study’s success. This not only helped keep the study on track when the client had changes to their own staff but provided a sense of consistency and reliability throughout the course of the trial at every level. Key roles project supervisor, project manager and other key staff stayed on for the whole of two years of study duration, something almost unheard of in this ever-changing industry. They are still with PSI running the trial as we write these lines.

The PSI Advantage

For the sixth year in a row, PSI CRO has been named a CRO Leadership Award winner in the categories of Expertise, Quality, and Reliability in the Overall (combined Big and Small pharma) respondent group. The CRO Leadership Awards are presented by Life Sciences Leader and Clinical Leader based on research conducted by ISR Reports. The awards recognize CROs that are voted by sponsors to meet or exceed expectations.

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral.

Oncology Experience

Including multiple myeloma, lymphomas, leukemias, and other oncohematological indications.

 

ASH 2023

Meet our team of experts at this year’s conference where we will be exhibiting at our booth #3352. 

 

Case Study: Optimizing Feasibility and Start-Up for a Phase III HemOnc Clinical Trial Read More »

radiopharmaceutical molecules, glass-like on an light blue background

Operationalizing Radiopharmaceutical Clinical Trials: Opportunities and Challenges  

When PSI published a blog post on the current state of radiopharmaceutical clinical trials in 2019, we had no way of knowing of the changes that would transform the clinical trial industry – along with every other one on earth – just a few months later.

Of course, managing global nuclear medicine trials has never been easy due to the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. However, travel restrictions and supply chain challenges have only exacerbated these obstacles. While some of these issues are starting to ease, the need for an experienced, global perspective toward managing these studies has only increased.

Success starts with understanding the risk factors that can impact your radiopharmaceutical trial from startup through the clinical phase. Drawing on our experience as we continue to run radiopharm studies in multiple oncology indications, we’ve highlighted some of the most common challenges to consider below – and how to overcome them.

1. Country-specific Regulatory Requirements for Radiopharmaceutical Agents

As development interest in this new class of agents has continued to grow, so has the complexity of the regulatory landscape. Additional approvals should be considered for studies in both the United States and the United Kingdom, as outlined in the table below:

Country Consideration
USA Radiation Safety Committees approvals typically obtained before submissions to IRBs
UK HRA radiology review prior to submission is needed, as well as approval of Administration of Radioactive Substances Advisory Committee (ARSAC). ARSAC review goes in parallel to the ethics/regulatory review

The European Union’s Clinical Trial Regulation has streamlined the process for submitting clinical trial applications in the EU, but many countries still encourage or require additional approvals. An in-depth understanding of each specific country’s requirements in your trial is essential to proactively anticipate requirements and potential questions that can delay approvals. Drawing on our experience with these studies, PSI maintains a library of country-specific radiopharmaceutical requirements and regulations within VISIONAL™, our machine-learning-powered system for data-driven feasibility and enrollment forecast. This pairing of regulatory expertise and technology allows us to accurately predict timelines and model hundreds of country and site combinations, their budgets, and probability of success within minutes.

2. Site Imaging Qualifications and Other Common Delays in Site Activation

Site qualification can be time-consuming for sites, so sponsors should confirm timelines during the feasibility process and ensure that sites are well-trained and supported with any study-specific calibration or camera requirements. PSI created the role of Site Support Specialist to help support sites in the qualification and camera process as well as during the study, saving them time and frustration. An example of the site imaging qualification process is shown below.

Site Imaging Qualifications

This is a simplified example, and the process can be much lengthier if dosimetry is included as part of the study. We have found having a dedicated Site Support Specialist assigned to work one-on-one with each site during the qualification process significantly decreases delays in site activation due to camera qualification.

Issues with technical transfer, or IND amendments (if the drug will be manufactured on-site), can also lead to delays. In some instances, choosing a central procurement facility may be effective, allowing one facility to execute the contract and technical transfer independent of site startup and activation.

3. Logistical Issues During Clinical Phase

As noted in our previous article, cooperation and coordination are imperative every step of the way for the successful delivery of radiopharmaceutical trials: from the facilities and procedures that produce the nuclear material to their handling and storage to the transportation of the drug and dispensation. Understanding the patient journey and which procedures must be completed at each step, including when the investigational product should be ordered, is recommended as a proactive foundational tool. At PSI, we have developed a detailed and unique visual patient journey utilized at the site and project levels.

In addition, other tools for clinical staff, such as a patient visit and MRI/whole brain PET scan tracker calendar, biopsy procedure schedule, source template, and automatic calculator for time-dependent procedures, will help provide additional clarity and compliance. We also recommend tracking key steps via Interactive Response Technology.

4. Central Radiology Review and Delays in Submitting Scans

It is critical to manage and track all steps in the imaging process at each site, including navigating the technical dialogue between nuclear medicine technologists, nuclear physicians/radiologists, investigators, and other stakeholders. Sponsors should ensure clear communication and receipts from the central reader for all scans received and that the appropriate project team members are copied on any queries to the site. PSI’s Site Support Specialist is key in ensuring every stage is performed accurately and on time, including monitoring site submissions in real time and assisting sites with submissions when needed. This role has also proven beneficial in managing and providing oversight of all site queries, cutting the site team’s time spent on imaging queries in half.

5. Development and Implementation of Site-Specific Enrollment Plans

Solid tumor oncology trials represent one of the most competitive markets in clinical research, with over 3,000 trials ongoing or planned, according to data from clinicaltrials.gov, Citeline, and GlobalData. With additional obstacles presented by sites’ limited proximity to manufacturing centers, sponsors and their partners should have detailed site-specific enrollment plans that consider the patient journey at each site, from identifying prospective patients to scheduling the needed imaging assessments and surgeries or biopsies. Walking through this patient journey helps both the site and the CRA to identify all the involved team members so that potential risk factors can be mitigated. PSI’s dedicated Site Support Specialists may meet with sites as soon as they’re selected by clients to understand this patient journey and put together a tailored site enrollment strategy based on site referral patterns, facilities, capabilities, and other key factors.

Meet the challenge of your radiopharmaceutical pivotal trial with PSI

Every study is different, and there is no one-size-fits-all solution for ensuring success. With an established and proven database of more than 1,000 global radiopharmaceutical sites, PSI specializes in delivering radiopharm studies on time and with quality data. Seventy-nine percent of PSI CRAs have oncology experience, and PSI has developed therapeutic-specific training and resources for radiopharmaceutical trials to achieve the highest level of quality for your study. In addition, PSI’s Site Support Specialist role has led to a dramatic improvement in site activation and enrollment.

Contact us here to learn more about running your pivotal Phase 2 and 3 radiopharmaceutical trials with PSI.

Operationalizing Radiopharmaceutical Clinical Trials: Opportunities and Challenges   Read More »

DNA on dark background

Clinical Research Breakthroughs Defining the Future of Oncology  

The 2022 American Society of Clinical Oncology (ASCO) Annual Meeting is one of the largest events for those professionals working in oncology in both clinical practice and research. While there was a significant focus on providing positive outcomes from trials, there were a few major ongoing or recently concluded studies that provided significant research discoveries based on their continued or lack of success.

Preparing for the Future of Oncology Clinical Research, co-authored by PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, provides essential insights for sponsors into the trends with the greatest potential to affect clinical trial design and operationalization. Read on to learn more about the general oncology trends to be aware of in 2023.

New insights into the influence of concomitant medications on immune checkpoint inhibitors

Immune checkpoint inhibitor (ICI) therapy is currently a standard of care for many malignancies. Recent findings suggest that the outcomes of ICI therapy may be influenced by concomitant medications that also have immunomodulatory properties, such as corticosteroids and antibiotics. Two study teams presented findings that explored the effects of concomitant use of acetaminophen and the live bacterial product CBM588 on ICI efficacy in cancer patients.

Antoine Italiano (Institute Bergonié, France) assessed the impact of acetaminophen use on immunotherapy efficacy in patients with different types of cancer.i The study showed that detectable plasma acetaminophen levels at treatment onset were associated with a worse clinical outcome in ICI-treated cancer patients and reduced treatment efficacy. Important unanswered questions remain, including the nature of the influence of the previous acetaminophen exposure, whether there is a difference between sporadic and chronic acetaminophen use, and whether there is any influence of acetaminophen on ICI-related toxicity.

The negative association between ICI response and concomitant antibacterial therapy is well defined. Nazli Diman (City of Hope Comprehensive Cancer Center, California, USA) investigated whether concomitant use of the live bacterial product CBM588 (a probiotic strain of bacteria that can restore species of Bifidobacterium to the microbiome) with ICI therapy could facilitate an improved response.ii The study enrolled patients with newly diagnosed metastatic renal cell carcinoma and showed that adding CMB588 to the standard treatment scheme with nivolumab/ipilimumab increased the objective response rate from 20% to 58%. The investigators suggested that CBM588 decreases antibiotic resistance, which is significant given the common use of antibiotics in cancer patients to treat infections.

dna in test tube

ctDNA as an Emerging Biomarker

Circulating tumor DNA (ctDNA) was first described in 1948, but the first clinical validation happened only when next-generation sequencing (NGS) technology was introduced in the 2000s.iii The symposium “ctDNA: Dawn of a New Era” at the 2022 conference discussed how this methodology is transforming the field of oncology.

During the past several years, liquid biopsy (detection of ctDNA through a simple blood draw) has gained much attention in clinical practice and clinical research. In May 2022, the U.S. Food and Drug Administration (FDA) released industry guidance on ctDNA testing when developing drugs for early-stage tumors.iv The guidance describes three potential uses for ctDNA:

  • Selecting patients for treatment based on molecular alterations
  • Monitoring tumor response at the molecular level via minimal residual disease to identify risk of recurrence
  • Acting as an early surrogate measure of long-term outcomes

The biggest challenge with ctDNA testing is that researchers still do not know whether intervening after a positive ctDNA result will improve patients’ outcomes like survival or quality of life. Multiple clinical trials aim to address this question, particularly what should be done in the case of a positive (or negative) ctDNA result.

Another therapeutic research focus was on ctDNA testing across multiple tumor types, including head and neck cancer, non-small cell lung cancer (NSCLC), breast cancer, soft tissue sarcoma, and oropharyngeal cancer. Based on the findings from these papers, we can conclude that:

  • ctDNA can be used for molecular profiling in patients with advanced solid tumors to guide therapeutic decisions
  • ctDNA has the potential to identify patients who have a molecular response to therapy at an early timepoint
  • Detection of ctDNA after curative therapy across many tumor types is strongly predictive of the likelihood of recurrence in many cases, and importantly, it occurs before radiographic or clinical progression.

The interpretation of ctDNA-negativity must follow the same pattern as for many diagnostic tests — ctDNA-negativity does not mean the disease is cured, but ctDNA-positivity does mean it is not cured.

Conclusion

While breakthrough technology and therapies drive much of the conversation in research, it is important to highlight the long-term effects of current treatments and therapies year-over-year. If you are interested in learning more about PSI’s in-depth experience with various oncology indications, check out our oncology therapeutic expertise page or contact us to learn how PSI can help you propel your phase 2 or 3 oncology study forward.

iItaliano, A., lsambert, N., Metges, J.-P., Toulmonde, M., Cousin, S., Pernot, S., Spalato, M., Grellety, T., Auzanneau, C., Lortal, B., Kind, M., Le Loarer, F., Sellan-Albert, S., u Bellera, C. A. (2022). Caire: A basket multicenter open-label phase 2 study evaluating the EZH2 inhibitor tazemetostat in combination with durvalumab in patients with advanced solid tumors. Journal of Clinical Oncology, 40(16_suppl), TPS2703-TPS2703 https://doi.org/10.1200/jco.2022.40.l6_suppl.tps2703

iiDizman, N., Meza, L.A., Bergerot, P. G., Dorff, T. B., Lyou, Y., Frankel, P.H., Llamas, M., Hsu, J., Zengin, Z. B., Malhotra, J., Govindarajan, A., Castro, D. V., Gillece, J. D., Reining, L. J., Trent, J.M., Takahashi, M., Oka, K., Higashi, S., Highlander, S. K., u Pal, S. K. (2022). Characterization of the microbial resistome in a prospective trial of CBM588 in metastatic renal cell carcinoma (MRCC) offers mechanism for interplay between antibiotic (abx) use and immune checkpoint inhibitor (ICI) activity. Journal of Clinical Oncology, 40(16_suppl), 4510-4510. https://doi.org/10.1200/jco.2022.40.l6_suppl.4510

iiiMandel, P. and Metais, P. (1948) Les acides nucl, eiques du plasma sanguin chez l’homme., C. R Seances Soc.Biol. Fil.142, 241-243.

ivOncology Center for Excellence. (2022, May). “Use of Circulating Tumor Deoxyribonucleic Acid for Early-Stage Solid Tumor Drug Development; Draft Guidance for Industry; Availability. U.S. Food and Drug Administration.” Retrieved July l, 2022, from https://www.fda.gov/regulatory-information/search-fda­ guidance-documents/use-circulating-tumor-deoxyribonucleic-acid-early­ stage-solid-tumor-drug-development-draft-guidance

vLipsyc-Sharf, M., De Bruin, E., Santos, K., McEwen, R, Stetson, D., Patel, A., Kirkner, G. J., Hughes, M. E., Tolaney, S. M., Krop, I.E., Knape, C., Feger, U., Marsico, G., Howarth, K., Winer, E. P., Lin, N. U., u Parsons, H. A. (2022). Circulating tumor DNA (ctdna) and late recurrence in high-risk, hormone receptor-positive, HER2-negative breast cancer (CHIRP). Journal of Clinical Oncology, 40(16_suppl). https://doi.org/10.1200/jco.2022.40.l6_suppl.103

Clinical Research Breakthroughs Defining the Future of Oncology   Read More »

3 Innovations Impacting Oncology Clinical Trials in 2023 & Beyond 

Each year, the American Society of Clinical Oncology (ASCO) Annual Meeting is held, bringing together professionals working together in oncology in both clinical practice and research. This year’s conference focused on innovations from a variety of oncologic therapeutic disciplines, highlighting research that has the greatest potential to change current clinical and therapeutic practices. PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, reviewed the abstracts presented to develop a comprehensive overview of the trends with the greatest potential to affect oncology clinical trial design and operationalization. Read on to learn about three of the most significant oncology innovations to be aware of from ASCO 2022. For the full report, download Preparing for the Future of Oncology Clinical Research, available now.

1. Breast Cancer Breakthrough: Doubling Progression-Free Survival in "HER2-low" Patients

Breast cancer is the most frequent malignancy in women, with an estimated 291,000 new cases expected in the United States in 2022.I While breast cancer is curable at early stages, advanced or metastatic cancer is still a significant therapeutic challenge.

As a rule, patients with advanced breast cancer featuring low human epidermal growth factor receptor 2 (HER2) expression levels are diagnosed with HER2-negative disease because HER2-targeted therapies are typically ineffective in this setting. The DESTINY-Breast04 trial upends this paradigm, opening the door to a new treatment option for the approximately 60% of patients referred to as “HER2-low” (IHC score of 0-1).ii In this double-blind Phase 3 trial, patients with HER2-low metastatic breast cancer treated previously with one to two prior lines of chemotherapy for metastatic disease were randomized to receive trastuzumab deruxtecan (a HER2-directed antibody and topoisomerase inhibitor conjugate) or the physician’s choice of standard chemotherapy.

The study showed that progression-free survival (PFS) was nearly double for trastuzumab deruxtecan versus standard chemotherapy (9.9 versus 5.1 months), and the overall survival (OS) was significantly better with trastuzumab deruxtecan compared with standard therapy (23.4 versus 16.8 months). Safety analysis did not identify new safety concerns and showed fewer treatment-emergent adverse events (TEAE) with trastuzumab deruxtecan than with standard chemotherapy (52.6% versus 67.4%).

These practice-changing findings establish patients with HER2-low metastatic breast cancer as a targetable population with trastuzumab deruxtecan as a new standard of care in this setting. DESTINY-Breast04 is the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer.

2. Trends in Hematological Oncology Clinical Trials: Exploring Comparative Therapies for Chronic Myeloid Leukemia

Many patients with chronic myeloid leukemia (CML) experience good survival outcomes from therapy with tyrosine kinase inhibitors (TKIs). However, 40-50% of these patients may need to change therapy due to disease progression or recurrence. Importantly, TKIs have different mechanisms of action, and the treatment effect depends on matching the drug and mutation.

The ASCEMBL trial is a Phase 3, randomized, multicenter study designed to explore whether asciminib is safe and effective for patients with CML compared with a commonly used ATP-binding TKI (bosutinib).iii Asciminib is a BCR-ABL1, first-in-class specifically targeting ABL myristoyl pocket (STAMP) inhibitor that differs from TKIs in its mechanism of action and ability to overcome mutations associated with TKI resistance. Primary analyses indicated that major molecular response (MMR) with asciminib exceeded MMR with bosutinib (25.5% versus 13.2%), and results at 48 weeks consistently favored asciminib over bosutinib in efficacy and safety. Analysis of efficacy and safety outcomes at 96 weeks showed that MMR with asciminib exceeded MMR with bosutinib by 21.7%. These results are important, as providers will likely start prescribing this medication now that it is approved.

3. Lung Cancer Clinical Trial Innovations: Finding the Ideal Therapeutic Combination for Resectable Stage IIIA NSCLC

Worldwide, lung cancer caused an estimated 1.8 million deaths in 2020.iv In the United States, there are over 230,000 new cases of lung cancer and 130,000 deaths annually.v

The results of the NADIM II study were presented by Mariano Provencio-Pulla, MD, PhD (Hospital Universitario Puerta de Hierro, Madrid, Spain).vi The study enrolled 86 patients who were randomly assigned to receive nivolumab plus carboplatin-based chemotherapy or chemotherapy alone. The primary endpoint was pathological complete response (pCR). The trial found that neoadjuvant nivolumab plus carboplatin-based chemotherapy improves pCR for patients with resectable stage IIIA NSCLC compared with chemotherapy alone: 36.8% versus 6.9%, correspondingly. The addition of nivolumab to chemotherapy did not significantly increase toxicity.

This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. It means that we can expect a change in the standard of care for these patients.

Conclusion

As the need for oncology clinical trials persists and grows, PSI CRO is committed to keeping abreast of the latest scientific advances and partnering with the companies doing the most exciting work across a wide range of oncology diseases. To learn more, download Preparing for the Future of Oncology Clinical Research today.

I Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2022). Cancer statistics, 2022. CA: A Cancer Journal for Clinicians, 72(1), 7–33. https://doi.org/10.3322/caac.21708

ii Modi, S., Jacot, W., Yamashita, T., Sohn, J., Vidal, M., Tokunaga, E., Tsurutani, J., Ueno, N. T., Chae, Y. S., Lee, K. S., Niikura, N., Park, Y. H., Wang, X., Xu, B., Gambhire, D., Yung, L., Meinhardt, G., Wang, Y., Harbeck, N., & Cameron, D. A. (2022). Trastuzumab deruxtecan (T-DXD) versus treatment of Physician’s Choice (TPC) in patients (PTS) with HER2-low unresectable and/or metastatic breast cancer (MBC): Results of destiny-breast04, a randomized, phase 3 study. Journal of Clinical Oncology, 40(17_suppl), LBA3-LBA3. https://doi.org/10.1200/jco.2022.40.17_suppl.lba3  

iii Rea, D., Mauro, M. J., Hochhaus, A., Boquimpani, C., Lomaia, E., Voloshin, S., Turkina, A. G., Kim, D.-W., Apperley, J., Cortes, J. E., Sasaki, K., Kapoor, S., Allepuz, A., Quenet, S., Bédoucha, V., & Minami, Y. (2022). Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (PTS) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIS): Week 96 update. Journal of Clinical Oncology, 40(16_suppl), 7004–7004. https://doi.org/10.1200/jco.2022.40.16_suppl.7004 

iv Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660 

v Lung cancer statistics: How common is lung cancer? American Cancer Society. (2022, February 14). Retrieved July 1, 2022, from https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html  

vi Provencio-Pulla, M., Nadal, E., Larriba, J. L., Martinez-Marti, A., Bernabé, R., Bosch-Barrera, J., Casal, J., Calvo, V., Insa, A., Aix, S. P., Reguart, N., Carpeño, J. D., Mosquera, J., Benitez, R., Aguado De La Rosa, C., Palmero, R., Hernando-Trancho, F., Romero, A., Cruz Bermudez, A., & Massuti, B. (2022). Nivolumab + chemotherapy versus chemotherapy as neoadjuvant treatment for Resectable Stage IIIA NSCLC: Primary Endpoint Results of Pathological Complete Response (PCR) from phase II Nadim II trial. Journal of Clinical Oncology, 40(16_suppl), 8501–8501. https://doi.org/10.1200/jco.2022.40.16_suppl.8501 

3 Innovations Impacting Oncology Clinical Trials in 2023 & Beyond  Read More »

PSI Publishes New Report on the Future of Oncology Clinical Research

PSI CRO AG, a full-service global CRO specializing in pivotal Phase 2 and 3 trials for oncology, hematology, and other select therapeutic areas, has published a new report on the current landscape of oncology research and its impact for future trials. Preparing for the Future of Oncology Clinical Research, co-authored by PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, provides essential insights for sponsors into the trends with the greatest potential to affect clinical trial design and operationalization.

Preparing for the Future of Oncology Clinical Research cover

Kosov and Zenzola de Toma reviewed data from over 2,200 poster presentations at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting to develop the comprehensive overview. Topics include:

  • General trends in oncology, including insights into concomitant medications’ impact on immune checkpoint inhibitors and emerging biomarkers such as ctDNA
  • Therapeutic advances in the most challenging indications, including “HER2-low” breast cancer and resectable stage IIIA NSCLC
  • Additional research highlights in gastrointestinal, gynecological, and genitourinary cancers as well as pediatric oncology and rare disease

“Oncology studies face unique challenges due to their expansive geographic footprints, lengthy screening and treatment durations, and massive amounts of clinical data,” said Dr. Kosov. “As the need for oncology clinical trials persists and grows, PSI CRO is committed to keeping abreast of the latest scientific advances and partnering with the companies and investigators doing the most exciting work across the wide range of oncology diseases.”

For the past 25 years, PSI CRO has worked with sponsors to advance their research in oncology by proactively cultivating long-term relationships with sites around the world and applying advanced technology for data-driven feasibility and enrollment forecast, including through its proprietary technology platform, INTELIA™.

VISIONAL™, the latest addition to the platform, allows project managers and sponsors to model and compare hundreds of country and site combinations, their budgets and probability of success within just a few minutes. In the end, it recommends the most optimal enrollment scenario in line with sponsor key objectives.

Preparing for the Future of Oncology Clinical Research is available now. For more information about how PSI plans and executes seamless oncology clinical trials with novel designs, click here.

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Strategies for Working with NGS Testing on Site in China

Did you know that NGS testing in China can be expedited with the right site relationships? 

As treatment options move towards enhanced personalization, NGS testing, or specific gene mutation testing, has become increasingly common as part of modern oncology and hematology clinical trials. When PSI Shanghai was contacted about a specific oncology trial requiring NGS testing, the team was able to contact 24 sites with relevant indication experience, and within 3 days, received interest from 15 of those sites to participate. 

In order to accelerate patient enrollment, PSI engages a trusted network of highly qualified sites to ensure that each trial’s needs are met with specific experience. Learn more about NGS testing in China with Lisa Lu, Country Manager.

If you have a phase 2/3 clinical trial requiring NGS testing, consider clinical trial sites in China. Around the world, PSI CRO is working to ensure studies deliver on time and on budget. Discover more about our oncology and hematology experience here or contact us to speak with an expert today.

Transcript:

Did you know the NGS testing status in China?
Modern Oncology and hematology trials often require specific mutation testing, as we all move to a more personalized
medicine in time.
While this NGS technology is well established in China, it is not used in every study yet.
We still have capacity here. Let me share with you some recent cases.
We recently had a request for a specific oncology trial to be run in China. The protocol required sites being able to run the
NGS testing in screening phase. PSI’s Shanghai team contacted 24 sites with study experience in this indication.
Overall, the sites’ attitude was positive.We only had 3 days to check our sites. Among all of them, 15 sites expressed immediate interest and had the relevant
NGS experience and equipment.
The results show that NGS testing is not a show stopper for any modern trials which need this measured in China.
Looking forward to seeing you in Shanghai.

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NSCLC Clinical Trials: History, Trends, and Opportunities

Lung cancer is one of the diseases that will never vanish from the radar of physicians, scientists, and society. However, there have been significant advances in our understanding and treatment of this disease over the past century, particularly for non-small cell lung cancer (NSCLC). In this white paper, we review the primary diagnostic and treatment options used today, the current trends, and their implications on the design and conduct of NSCLC clinical trials.

Based on PSI CRO’s experience with more than 25 Phase 2 and 3 clinical trials in advanced and metastatic NSCLC during the past ten years, we have experience overcoming several major challenges of these studies. To learn more about how we can support your upcoming NSCLC clinical trial, contact us today.

NSCLC Clinical Trials: History, Trends, and Opportunities Read More »