Signature program: a platform of basket trials

Area of Science:

• Oncology
• Clinical Pharmacology
• Genomics

Background:

• Investigating targeted therapies is complex due to tumor heterogeneity and slow clinical trial accrual.
• The Signature Program aimed to overcome these challenges using a novel, rapid study design.

Purpose of the Study:

• To evaluate the efficacy of 8 different targeted agents across various solid and hematologic malignancies with actionable mutations.
• To assess the feasibility of a rapid, decentralized study start-up approach for early-phase oncology trials.

Main Methods:

• A series of 8 phase 2, agent-specific basket protocols were implemented.
• No predetermined study sites were used, allowing for rapid initiation across 192 US sites.
• Clinical benefit rate (response or stable disease at 16 weeks) was the primary endpoint.

Main Results:

• The median study start-up time was 3.6 weeks.
• 595 patients with common mutations (e.g., PIK3CA, RAS) in various cancers (colorectal, lung, ovarian) were treated.
• 30 partial or complete responses were observed with 6 agents across 16 tumor types.

Conclusions:

• The Signature Program demonstrated a successful and unique approach for rapid signal finding in targeted cancer therapy.
• This model facilitates the evaluation of agents in patients with rare genetic alterations, potentially improving trial efficiency and patient outcomes.