Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)

• Status: Not yet recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Panitumumab is in a class of medications called monoclonal antibodies. It works by slowing or stopping the growth of cancer cells. Giving combination panitumumab and sotorasib may kill more tumor cells in patients with advanced solid tumors with KRAS G12C mutation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulins; Panitumumab

Criteria

Inclusion Criteria:

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-E5 based on the presence of an actionable mutation as defined in EAY191

• Patient must be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration/randomization to the EAY191-E5 study

• Patient must be >= 18 years of age

• Patient must have a KRAS G12C alteration as determined by the ComboMATCH screening assessment

• Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have tissue available from within 12 months prior to EAY191-E5 registration

• Patient must have histologically confirmed advanced/metastatic solid tumor

• Patient must have progressed on at least one line of standard of care therapy.

• NOTE: Patients who have progressed on a prior human epidermal growth factor receptor (EGFR) inhibitor will meet this criterion

• Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2 (or Karnofsky Performance Status > 60%)

• Patient must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

• Patient must have the ability to retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption

• Patient must have completed full treatment cycle prior to EAY191-E5 registration/randomization if they have received prior chemotherapy, biological cancer therapy, radiation therapy or an investigational agent/device. Patients must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from any adverse events due to prior cancer therapy (with the exception of alopecia).

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

• Human immunodeficiency virus (HIV)-infected patients no effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac history, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trail, patients should be class 2B or better

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase ([SGPT]) < 3 x institutional upper limit of normal

• Creatinine =< 1.5 x institutional ULN OR creatinine clearance > 50 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 mg/dL

• COHORT II: Patient must have progressed after treatment at the recommended phase II dose (RP2D) of any KRAS G12C inhibitor

Exclusion Criteria:

• Patient must not have any serious active infection within 4 weeks prior to EAY191-E5 registration/randomization (e.g., requiring hospitalization and/or intravenous [IV] antibiotics) or currently receiving oral or IV antibiotics for the treatment of infection. Patients receiving prophylactic antibiotics are eligible

• Patient must not have any history of or current evidence of non-infectious interstitial lung disease (ILD)/pneumonitis

• Patient must not have a history of allergic reactions attributed to either of the study agents or to agents of similar chemical or biologic composition

• Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 6 months after the last dose of protocol treatment. Patients must not breastfeed while receiving protocol treatment and for one week (7 days) after the last dose of AMG 510 (sotorasib) and 2 months after the last dose of panitumumab

• COHORT I: Patient must not have colorectal cancer or non-small cell lung cancer

• COHORT I: Patient must not have been previously treated with a KRAS G12C inhibitor

• COHORT II: Patient must not have been previously treated with a KRAS G12C inhibitor in combination with an EGFR inhibitor