A Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab

Sponsor
Korea University Anam Hospital
Study ID
NCT05993455
Phase
PHASE2
Status
Unknown

Conditions

  • Efficacy

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Oral sotorasib + IV Panitumumab — DRUG
    Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (\> 1,000 mg).

Study Details

Kirsten rat sarcoma (KRAS) mutation is one of the most common genetic mutations associated with tumor development in various human cancers, including pancreatic cancer, non-small cell lung cancer, and colorectal cancer. Previous studies have shown that KRAS mutations are present in approximately 70% of pancreatic cancer patients, 35% of colorectal cancer patients, 20% of non-small cell lung cancer patients, and 15% of cervical cancer patients. Patients with KRAS mutations generally have a shorter overall survival and increased resistance to treatment compared to wild-type tumors. KRAS mutations have been known for decades, but they have been considered "undruggable" as effective therapies targeting them were lacking. Preclinical studies focusing on colorectal and non-small cell lung cancer cell lines have suggested that colorectal cancer cell lines exhibit a stronger response to EGFR signaling and activation of multiple RTKs (Receptor Tyrosine Kinases) than non-small cell lung cancer cell lines. As a result, they show poorer responses to KRAS G12C inhibitors, leading to the development of initial and acquired resistance to KRAS G12C inhibition. Based on this hypothesis, a phase 1-2 clinical trial, known as the KRYSTAL-1 study, was conducted in patients with metastatic colorectal cancer. The study demonstrated that the objective response rate was 19% with adagrasib monotherapy and 46% with the combination of adagrasib and cetuximab (an EGFR inhibitor), indicating that the addition of an EGFR inhibitor can overcome resistance. Building on this hypothesis, a phase 3 trial is currently underway for KRAS G12C inhibition plus EGFR blockade in metastatic colorectal cancer (ClinicalTrials.gov identifiers: NCT04793958, NCT05198934). In this study, the aim is to investigate the efficacy of sotorasib (KRAS G12C inhibitor) plus panitumumab (EGFR inhibitor) in patients with advanced solid tumors harboring KRAS G12C mutations, who have failed standard treatments.

Key Dates

Start date
Jul 3, 2023
Status verified
Aug 2023
Primary completion
Sep 4, 2023
Completion
Dec 31, 2023

Study Design

Enrollment
24 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Oral sotorasib + IV Panitumumab
    Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (\> 1,000 mg).

Primary Outcome Measure

Objective response rate based on RECIST v1.1 [ Time Frame: Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days). ]

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