In short

  1. Clinical trials in the highly-active melanoma therapeutic area are difficult to run. Sponsors face challenges ranging from timely identification of the right patients to make the trial stand out in a crowded landscape, to dealing with evolving standards of care (meaning trial data may lose relevance by study end)
  2. A sponsor partnered with PSI to run their mid-phase personalized immunotherapy trial for high-risk melanoma. Our goal is to execute their trial flawlessly so the sponsor maintains their competitive edge, and that potentially life-changing treatments reach patients as efficiently as possible
  3. Early site alignment and tailoring the study processes to site realities helped ensure sites were prepared to enroll patients
  4. Simplifying patient screening workflows and tightening logistics by country CRAs further reduced operational challenges
  5. The trial is meeting its milestones on time

The challenge

A biopharma sponsor chose PSI to manage their innovative, personalized immunotherapy-based clinical trial for melanoma across multiple treatment settings. With the sponsor’s novel and complex protocol, PSI has helped them stay on track and achieve key milestones on time through proactive planning, streamlined communication and operational excellence. Read on for PSI’s suggestions and guidance to running complex melanoma trials on time.

The operational landscape of melanoma trials

Melanoma develops from melanocytes (cells in the lower epidermis responsible for skin pigmentation) which become malignant, typically due to DNA damage [1]. Most common in adults [2, 3], melanoma is usually diagnosed by biopsy following an initial skin exam [4]. Melanoma is among the more common cancers (despite a smaller proportion of overall cancer cases compared with lung, breast, prostate, or colorectal) [5]. Within skin cancers, melanoma is the most serious – it is responsible for the majority of deaths, despite being less common than basal cell, or squamous cell carcinoma [6]. The incidence of melanoma has risen for decades [2] and is highest among fair-skinned populations living in warm, sunny climates (Australia has the highest melanoma incidence worldwide [2]).

Beyond the challenges associated with any oncology study (primarily rapid disease progression preventing patients from enrolling), melanoma clinical trials are deceptively complex. Sponsors must take these factors into account:

  1. How to find patients with melanoma: The incidence of melanoma has been increasing steadily in many regions, largely due to UV exposure and better detection. Australia is the obvious answer for melanoma trial enrollment, but for highly personalized studies, forms just one component. A sophisticated country strategy for melanoma is going not where the most patients exist, but where the fewest patients are lost operationally between diagnosis and individualized treatment initiation. Many melanoma patients are not initially treated at major academic centers, often starting in community dermatology or oncology practices, before later moving to tertiary care
  2. For advanced therapy trials, how to find sites capable of operational execution: Operational execution extends beyond the oncology clinic, involving surgery, pathology, molecular diagnostics, complex laboratory needs, and sequencing infrastructure. If operational execution fails, there is no personalization and most importantly, there is no treatment.
  3. How to differentiate the trial from current SoC: Treatment for early-stage melanoma is quite effective (resection and/or immunotherapy). While metastatic melanoma remains difficult to treat, combination immunotherapy [7] and targeted therapy [8] have been repeatedly demonstrated to improve patient outcomes. Focusing on subsets not fully addressed by current therapies, or novel mechanisms, is key
  4. How to cope with evolving SoC: In the rapidly evolving melanoma therapeutic landscape [9], advances in checkpoint inhibitors, earlier intervention approaches, and novel therapies (mRNA and TIL approaches, among others) mean continuous feasibility is required to make sure the data remains relevant in the therapeutic landscape at the end of the trial
  5. How to make sure investigators are invested: Pharma investment in melanoma is high, and there are many competing trials for drugs with similar mechanisms (e.g., PD-1, LAG-3, or CTLA-4) [9]. Investigators have their pick of trials, and will choose those that show promise for their patients, or provide their sites with additional benefit
  6. How to avoid restrictive protocols: In melanoma, eligibility criteria are becoming increasingly narrow (e.g., BRAF mutation status requirements or prior exposure restriction/constraints) [10]. While tightly-written protocols can control risk and enhance data quality, this limits recruitment. Targeting unmet needs and maximizing safety can ensure smooth recruitment and easy trial completion

For a successful trial in melanoma, sponsors must work with the right, forward-thinking CRO, so their study isn’t lost in the crowd, and is executed on time.

The solutions

Against this background, the solutions to the sponsor’s trial had a dual focus: optimizing site activities quickly and effectively, and streamlining trial operations. Strong execution from the onset is what leads to on-time delivery.

  • Early site alignment
    • Established strategic collaboration with sites prior to study initiation to gain substantial momentum
    • Mapped out the care pathway in each region, identifying the dermatologists, Mohs surgeons, surgical oncologists, community oncologists, and pathology groups to create rapid referral into trials. Pre-trial screening was offered as a service to community practices
    • Partnered with pathology labs and genomic testing vendors to create alerts when eligible patients are identified via biomarker screening
    • Adapted workflows based on key infrastructure needs at a country, site- and patient-level, so trial processes worked smoothly, from the pre-SIV phase of site setup through treatment procedures
  • The local approach to site training and communication
    • Activated regional dermatologists (an underutilized referral source) and broader dermatology networks to increase enrollment rates
    • Educated regional dermatologists on clinical trials within their area, and provided trial awareness packages (with referral decision trees) and structured training sessions covering protocol requirements for personalized immunotherapy, operational expectations, and documentation/compliance
    • Developed a comprehensive logistics checklist that guided processes from participant identification through treatment, thus ensuring queries were addressed proactively before impacting enrollment or milestones, and increasing transparency of communication between sites, sponsor, and the project team
    • Equipped site staff with the practical tools to execute the protocol efficiently from the study’s beginning
    • Distributed process-specific email templates in advance to guide sites from participant identification through treatment, and prompted sites to confirm planned treatment dates and verify the availability of required supplies, thus ensuring smooth coordination and preparedness across all study phases
  • Finding efficiencies in screening and enrollment
    • Designed simplified and efficient patient screening workflows, reducing administrative burden while maintaining protocol rigor
    • Created clear escalation pathways and continuous feedback loops to highlight and anticipate any emerging issues or risks
  • Highly orchestrated trial logistics and management
    • Planned for the delivery of all essential study materials in line with milestones, preventing operational bottlenecks
    • Deployed dynamic strategy monitoring to allow real-time adjustment of enrollment strategies based on site feedback

Key takeaways

Strong execution at the site level means hitting the trial milestones on time. Sponsors stay ahead of schedule when site strategy is fully realized and deliberate, logistics are synchronized, and performance is actively managed. Choosing a CRO that builds partnerships early and manages proactively throughout the trial protects your timelines – even before there is a potential risk.

PSI – your go-to CRO for complex pivotal oncology trials

Learn more

Abbreviations

BRAF, B-Raf proto-oncogene;
CRA, Clinical Research Associate;
CTLA-4, Cytotoxic T-lymphocyte associated protein 4;
LAG-3, Lymphocyte activation gene 3;
PD-1, Programmed Death-1;
SIV, site initiation visit;
SoC, standard of care.

References

1. Elder, D.E., et al., The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway. Arch Pathol Lab Med, 2020. 144(4): p. 500–522.
2. Saginala, K., et al., Epidemiology of Melanoma. Med Sci (Basel), 2021. 9(4).
3. Zhang, K., et al., Examining Demographic, Geographic, and Temporal Patterns of Melanoma Incidence in Texas From 2000 to 2018: Retrospective Study. JMIR Cancer, 2025. 11: p. e67902.
4. Lauters, R., Brown, A.D., and Harrington, K.A., Melanoma: Diagnosis and Treatment. Am Fam Physician, 2024. 110(4): p. 367–377.
5. Bray, F., et al., Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024. 74(3): p. 229–263.
6. Wang, M., Gao, X., and Zhang, L., Recent global patterns in skin cancer incidence, mortality, and prevalence. Chin Med J (Engl), 2025. 138(2): p. 185–192.
7. Knight, A., Karapetyan, L., and Kirkwood, J.M., Immunotherapy in Melanoma: Recent Advances and Future Directions. Cancers (Basel), 2023. 15(4).
8. Imani, S., et al., The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies. Front Oncol, 2024. 14: p. 1504142.
9. Kato, H., Drug Therapy for Melanoma: Current Updates and Future Prospects. Cancers (Basel), 2026. 18(3).