Oncology clinical trials have unique endpoints different from other therapeutic areas. Early development, which typically includes Phase I and II studies, is designed to determine the safety and efficacy of new treatments in a smaller patient population before moving on to larger, more definitive studies.
The endpoints in early-phase and late-phase oncology trials tend to differ significantly. The primary endpoint in early-phase trials is most often safety and tolerability, with the objective of determining the maximum tolerated dose (MTD) of the drug and identifying any dose-limiting toxicities (DLTs).
Whereas the secondary endpoints may include pharmacokinetics (PK) and pharmacodynamics (PD) data, to help generate insights on how the drug is absorbed, distributed, metabolized, and eliminated by the body, as well as the effects on target tissues. Especially Phase II studies may help measure preliminary efficacy parameters, such as tumor response rate (RR), Overall Response Rate (ORR), or Progression-Free Survival (PFS). Although, these may not be primary endpoints at this stage as the focus is to determine whether the treatment is safe enough to proceed to later phase trials.
To maximize outcomes from early phase studies, determining endpoints based on the study design, type of cancer, and the type of treatment being evaluated, can be crucial.
Some common endpoints used in early-phase oncology trials include:
- Safety and Tolerability: Safety is the primary concern in early-phase oncology trials. Adverse events (AEs) and serious adverse events (SAEs) are monitored closely to determine the safety and tolerability of the treatment. The most common toxicity grading system used is the Common Terminology Criteria for Adverse Events (CTCAE).
- Pharmacokinetics (PK): PK studies are used to determine how the body absorbs, distributes, metabolizes, and excretes the drug. PK endpoints may include measures such as maximum concentration (Cmax), time to reach maximum concentration (Tmax), and area under the curve (AUC).
- Pharmacodynamics (PD): PD studies are used to determine how the drug affects the tumor or cancer cells. PD endpoints may include measures such as Tumor Response Rate (RR), Progression-Free Survival (PFS), Overall Survival (OS), and Duration Of Response (DOR).
- Biomarkers: Biomarkers are used to identify patients who are most likely to benefit from the treatment or to monitor the response to treatment. Biomarker endpoints may include measures such as the expression of a specific gene or protein, circulating tumor cells, or imaging markers.
Recently, adaptive clinical trial designs in oncology are gaining more acceptance with regulators. The purpose of a multistage adaptive clinical trial design is to collect more meaningful data in the early development stage itself. However, they continue to require considerable planning, meticulous strategy development, and statistical expertise.
If you are an emerging oncology biotech planning your early-phase studies, the right statistical expertise can help you get ahead of potential late-stage challenges.
Algorics will be at ASCO 2023 held from June 2-6 at McCormick Place, Chicago, IL. To meet with our Founder and CEO, Nithiya Ananthakrishnan, write to us at hello@algorics.com