3 Innovations Impacting Oncology Clinical Trials in 2023 & Beyond 

By Dr. Maxim Kosov

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.


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