Guest Column | September 23, 2025

3 Ways Biotechs Can Relieve The Burden Of Their First Clinical Trial

By Katia Schlienger, MD, Ph.D., chief medical officer, Celex Oncology Innovations, Ltd.

Team building-GettyImages-869922148

Small biotech companies face significant challenges when advancing new drugs from early development into clinical trials, especially in oncology. While they often partner with CROs for Phase 1/2, first-in-human, Phase 2b/3, or RWE studies, this approach is not ideal as biotechs, which must ensure patient safety first, have to establish a parallel internal framework to oversee the CRO (biotechs retain full regulatory responsibility when working with CROs).

This oversight demands substantial internal expertise and a significant expansion of their organization to address additional governance structures. Specifically, small biotechs lack the infrastructure to oversee CRO-run trials, requiring the hiring of new teams for project management, operations, quality control, regulatory compliance, safety monitoring, biomarker strategy, analytics, and clinical site management - functions larger pharmaceutical companies typically manage in-house. Furthermore, managing multiple vendors, ensuring data integrity across different systems, navigating fragmented trials, and coordinating with external oversight bodies, such as data and safety monitoring boards (DSMBs), all add considerable complexity and inefficiency.

Adaptive trial designs, which permit planned modifications in response to ongoing trial data, together with real-world evidence (RWE) approaches, promise to soften some of these burdens – for example, by improving trial flexibility, better aligning the trial protocol with patients’ actual care settings, and boosting evidentiary support for regulatory and commercial decision-making. Yet, adopting adaptive trials and integrating RWE still require robust oversight, regulatory clarity, and organizational capacity — issues small biotechs must address to benefit from these evolving methods.

What Is The Alternative To CRO Outsourcing?

Nonprofit organizations are vital to clinical trials, acting as key enablers by funding research, providing patient resources, and advocating for specific diseases. These groups often offer financial support, educational materials, and robust support networks for both patients and researchers. Some organizations even conduct trials themselves or collaborate with institutions to advance medical knowledge.

Recently, partnerships with nonprofit organizations and government-funded organizations conducting platform trials in specific indications have gained traction. Large pharmaceutical companies are already leveraging these collaborations to identify promising drug signals in niche cancer types outside their core strategic focus.

Two recent examples include the Cancer Therapy Evaluation Program overseeing the National Cancer Institute’s (NCI) National Clinical Trials Network and funding the U.S. cooperative groups (SWOG; ECOG/ACRIN; Alliance, NRG, GOG). This example includes the development of Novartis' imatinib (GLEEVEC) in GIST via NCI Cooperative Groups (e.g., SWOG/CALGB).1 The other example includes platform trials like I-SPY2, where Merck's blockbuster drug pembrolizumab (KEYTRUDA) was initially identified as a promising agent for high-risk triple-negative breast cancer and was later confirmed in the pivotal Phase 3 KEYNOTE-522 trial, showcasing the significant impact of nonprofit-led platform trials on oncology drug development.2,3,4

However, biotech is lagging behind in utilizing these opportunities. This is where nonprofit- or government-led adaptive trials can offer several distinct advantages to biotechs, including:

  • Established infrastructure: Existing trials are already underway based on previously established designs.
  • Expert involvement: KOLs are often involved in study design from inception to completion.
  • Preapproved frameworks: Regulatory agencies, institutional review boards (IRBs), and independent ethics committees (IECs) have often already approved the design, patient population, endpoints, and statistical analysis.
  • Operational readiness: With scientific committee reviews complete and clinical sites already established, the time to first patient enrolled is accelerated.

These efficiencies, including cost-sharing and centralized activities, lead to considerable savings in time and resources. This "lean” development approach is also highly attractive to investors, accelerating the path to patient benefit.

Key Advantages Of Adaptive Clinical Trials

Building on the efficiency and translational power of nonprofit‑led platform trials, oncology research has increasingly shifted toward adaptive clinical designs.5 Since the pioneering BATTLE program at MD Anderson Cancer Center from 2006 to 2009, cancer treatment has changed from a "one-size-fits-all" approach to personalized therapies.6

Initially led by cancer and research centers, adaptive trial designs have quickly gained widespread adoption by government bodies, academic institutions, and Big Pharma. Many investigator-initiated precision oncology clinical trials were launched between 2010 and 2016 by organizations such as the NCI (e.g., NCI-MATCH, MPACT), clinical trial groups (e.g., Lung-MAP), and international bodies, including the American Society of Clinical Oncology (ASCO) (e.g., TAPUR), the Netherlands Cancer Institute (e.g., DRUP), and the European Organisation for Research and Treatment (e.g., CREATE).7 More recently, innovative data from PanCAN Precision Promise as well as those from GBM AGILE (GCAR) demonstrated the benefit of adaptive clinical trials.8,9,10

Adaptive randomization assesses the efficacy and safety of cancer treatments more rapidly and efficiently. From the small biotech perspective, an adaptive seamless design could accelerate regulatory approval for new anticancer agents, with a more accurate assessment requiring fewer patients overall within a single Phase 2/3 trial. Regulatory agencies such as the FDA have also issued guidelines to support these new trial methodologies.11

Insights From Real-World Evidence

Traditionally, drug development first begins with preclinical studies, using several key approaches: (i) correlating receptor expression (mutated or wild-type) on tumor cells with prognosis; (ii) testing new drug activity on established cancer cell lines; (iii) conducting ex-vivo experiments with autologous human systems (e.g., for immunotherapy); and (iv) assessing new agents or combinations in in-vivo animal models (e.g., human tumors in nude mice).

These preclinical experiments provide the initial evidence of the safety and efficacy of a new drug. This crucial information is essential for gaining regulatory approvals from bodies like the FDA, securing IRB and IEC approvals, and fostering investigator confidence and involvement before administering the drug to patients in clinical trials.

The widespread adoption of electronic medical records has revolutionized drug development by making vast amounts of cancer patient data retrospectively available. This enables RWE studies to identify potential associations between treatments and patient outcomes or prognosis, often revealing unexpected signals. However, these signals still require verification through prospective randomized trials, as retrospective RWE studies are observational and prone to bias.

New data illustrate the potential for retrospective studies in providing valuable insights: several retrospective RWE studies on checkpoint inhibitors combined with chemotherapy for first-line treatment in metastatic non-small cell lung cancer observed a statistically significant survival benefit (progression-free and overall survival) when treatment was administered in the morning versus the afternoon. This intriguing finding was recently confirmed by a prospective randomized Phase 3 trial presented at ASCO 2025, poised to change clinical practice for administration of immunotherapy for lung cancer and, potentially, for other indications.12,13,14

In essence, while only prospective trials lead to regulatory approval, RWE is proving to be an invaluable tool. It helps us to de-risk planned clinical trials and discover new therapeutic signals from both novel and existing drugs to identify their potential use in more refined patient populations.

Streamlined Biotech Nonprofit Collaborations & RWE Insights

Collaborations between small biotechs and nonprofit organizations offer a leaner, more efficient, and cost-effective path to accelerate cancer drug development. Nonprofit-led platform trials offer a robust infrastructure for small biotech innovators. This enables them to rapidly generate randomized, registrational data through adaptive seamless Phase 2/3 trials, significantly reducing their operational burden. Adaptive trials and further benefits allow early stopping for ineffective arms, shift focus to the most promising treatments, adjustment of sample sizes, and improved ethical oversight. Additionally, RWE studies offer valuable retrospective data that can inform and support prospective clinical trials, improving trial design, external validity, and helping regulators and payers see how therapies perform in real-world settings.

References:

  1. ANSHER, S.S. and SCHARF, R. (2006) ‘The Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute’, Annals of the New York Academy of Sciences, 949(1), pp. 333–340. Available at: https://doi.org/10.1111/j.1749-6632.2001.tb04041.x.
  2. Nanda, R. et al. (2020) ‘Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial’, JAMA Oncology, 6(5), pp. 676–684. Available at: https://doi.org/10.1001/jamaoncol.2019.6650.
  3. Campbell, M.J. et al. (2024) ‘Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer’, Cell Reports Medicine, 5(11), pp. 101799–101799. Available at: https://doi.org/10.1016/j.xcrm.2024.101799.
  4. Schmid, P. et al. (2024) ‘Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer’, New England Journal of Medicine, 391(21). Available at: https://doi.org/10.1056/nejmoa2409932.
  5. Berry, D.A. (2011) ‘Adaptive clinical trials in oncology’, Nature Reviews Clinical Oncology, 9(4), pp. 199–207. Available at: https://doi.org/10.1038/nrclinonc.2011.165.
  6. Platz, E.A. et al. (2011) ‘A novel two-stage, transdisciplinary study identifies digoxin as a possible drug for prostate cancer treatment’, Cancer Discovery, 1(1), pp. 68–77. Available at: https://doi.org/10.1158/2159-8274.CD-10-0020.
  7. Ha, H. et al. (2024) ‘Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design’, Cancer Research and Treatment, 56(4), pp. 991–1013. Available at: https://doi.org/10.4143/crt.2024.128.
  8. Picozzi, V.J. et al. (2022) ‘Precision Promise (PrP): An adaptive, multi-arm registration trial in metastatic pancreatic ductal adenocarcinoma (PDAC).’, Journal of Clinical Oncology, 40(16_suppl), pp. TPS4188–TPS4188. Available at: https://doi.org/10.1200/jco.2022.40.16_suppl.tps4188.
  9. Global Coalition for Adaptive Research (GCAR), 2019. GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II/III Response Adaptive Randomization Platform Trial Designed to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (NCT03970447). ClinicalTrials.gov [online]. Posted 30 July 2019. Available at: https://clinicaltrials.gov/study/NCT03970447 Accessed August 2025.
  10. Picozzi, V.J. et al. (2025) ‘Pamrevlumab plus nab-paclitaxel/gemcitabine (Pam + GA) as first- and second-line therapy in metastatic pancreatic cancer (mPDAC): Results from Precision Promise (PrP) Bayesian platform trial.’, Journal of Clinical Oncology, 43(4_suppl), pp. 673–673. Available at: https://doi.org/10.1200/jco.2025.43.4_suppl.673.
  11. Center (2020) Adaptive Designs for Clinical Trials of Drugs and Biologics Guidance, U.S. Food and Drug Administration. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry. Accessed August 2025.
  12. Catozzi, S. et al. (2024) ‘Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: An In-depth chronotherapeutic study’, European Journal of Cancer, 199, p. 113571. Available at: https://doi.org/10.1016/j.ejca.2024.113571.
  13. Zhu, G.-Q. et al. (2018) ‘Comparative efficacy and safety between ablative therapies or surgery for small hepatocellular carcinoma: a network meta-analysis’, Expert Review of Gastroenterology & Hepatology, 12(9), pp. 935–945. Available at: https://doi.org/10.1080/17474124.2018.1503531.
  14. Huang, Z. et al. (2025) ‘Overall survival according to time-of-day of combined immuno-chemotherapy for advanced non-small cell lung cancer: a bicentric bicontinental study’, EBioMedicine, 113, pp. 105607–105607. Available at: https://doi.org/10.1016/j.ebiom.2025.105607.

About The Author:

Katia Schlienger, MD, Ph.D., chief medical officer at Celex Oncology Innovations, Ltd., brings nearly two decades of experience in oncology drug and vaccine development.

Her career highlights include a 15-year tenure at Merck & Co. Inc., where she led early- and late-stage clinical programs for oncology and vaccines. She has also held various leadership roles at small biotechs, where she successfully advanced key pipeline programs in oncology, biologics, and infectious diseases. She was previously a research assistant professor at the University of Pennsylvania.

Dr. Schlienger earned her MD in clinical pathology from Lariboisière Saint-Louis and Rouen University hospitals and a Ph.D. in microbiology, virology, and immunology from the Pasteur Institute in Paris, France. Her expertise in clinical research, regulatory strategy, and translational research establishes her as a leader in therapeutic innovation.