A phase II basket trial of (IP) plus (drug) in patients with advanced gastrointestinal cancers and MAPK
pathway mutations

A Phase II Open-Label, Safety And Preliminary Efficacy Study Of [IP] In Combination With [IP] In Patients With Advanced Malignancies Who Have Progressed On [X, prior therapy]

Targeted Clinical Indications

• Basket 1: Cholangiocarcinoma;
• Basket 2: Pancreatic adenocarcinoma;
• Basket 3: Colorectal adenocarcinoma;
• Basket 4: Esophageal adenocarcinoma, esophageal squamous cell carcinoma, or GEJ adenocarcinoma;
• Basket 5: Gastric adenocarcinoma

Trial Design

• Basket design with each basket operating as a Simon two-stage design and open to enrollment in two stages.
• Stage 1 opened to an enrolment of 13 patients in each basket. After 13 patients enrolled in a single basket, enrollment is placed on hold for the evaluation of efficacy. If ≥ 4 patients in a basket achieve a response, then that specific basket opens to Stage 2 of enrollment. The decision to open a basket to Stage 2 is made by the sponsor following SMC approval.
• Stage 2 expands enrollment of each basket with additional patients.

Sites and Dates

• Up to 25 sites / 215 patients
• 2020-Present

Products

• Inhibitors

Challenges with Mitigations

• Product (drug) availability was at risk due to high demand; Aixial Group identified a vendor that could supply (drug) and (drug) product was purchased in advance to ensure availability to patients for trial participation
• COVID site challenges with start-up; Aixial Group worked closely with sites to ease the burden of start-up while they experienced staffing shortages during COVID waves.  Examples of the steps taken include providing pre-filled documents that required review and signature only, scheduled 1:1 site calls with the various site departments to work through contract and budget revisions, ICF updates, etc. to eliminate multiple back-and-forth exchanges, and provided flexibility in scheduling SIVs (e.g., multiple sessions to accommodate site team availability).

Successes

• Quicker than expected enrollment in Basket 2 (Pancreatic adenocarcinoma)
• Strong Sponsor/CRO/Site relationships
• Collaborative and thorough Site Initiation Visits leading to increased study knowledge by PI and site study team members resulting in a low screen failure rate and minimal protocol deviations
• Complex logistics with multiple vendors that could pose a risk to endpoints have been mitigated by the implementation of a customized logistics management tool and dedicated team member leading to increased compliance with protocol specimen collection, as well as proper, on-time shipping and delivery of specimens to multiple laboratories
• Upfront collaboration with the sponsor on the scope of services and projected effort for effective and efficient project management and delivery has led to a very limited need for change orders (those in effect have been sponsor-driven requests for additional services)
• Sponsor audit with no major findings