Avutometinib + Sotorasib for Lung Cancer
(RAMP203 Trial)
Recruiting in Palo Alto (17 mi)
+33 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Verastem, Inc.
Must not be taking: CYP3A4 inhibitors
Disqualifiers: Prior malignancy, Brain metastases, Heart disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with sotorasib with or without defactinib in patients with KRAS G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.
Will I have to stop taking my current medications?
The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers (types of drugs that affect how your body processes medications) at least 14 days before starting the study and during the trial. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Avutometinib + Sotorasib for lung cancer?
Sotorasib has been shown to be effective for treating non-small cell lung cancer (NSCLC) with a specific KRAS mutation, with a 36% response rate in patients who had already tried other treatments. This suggests that sotorasib, as part of the combination with Avutometinib, may offer benefits for similar lung cancer cases.
12345Is the combination of Avutometinib and Sotorasib safe for humans?
Sotorasib, also known as Lumakras, has been approved for treating certain lung cancers and is generally considered safe, though common side effects include diarrhea, muscle pain, nausea, fatigue, liver issues, and cough. There is no specific safety data available for the combination of Avutometinib and Sotorasib, but Sotorasib alone has a manageable safety profile.
12367What makes the drug Avutometinib + Sotorasib unique for lung cancer?
The combination of Avutometinib and Sotorasib is unique because it targets KRAS G12C mutations in non-small cell lung cancer (NSCLC), with Sotorasib being the first approved drug specifically for this mutation. This combination may offer a new option for patients who have already undergone other treatments.
12348Eligibility Criteria
This trial is for adults with a specific mutation in their lung cancer (G12C KRAS). They must have tried some treatments but not more than two, and can't have used a KRAS inhibitor if they want to join certain parts of the study. Participants need good organ function, no recent other cancers or severe illnesses, and agree to use birth control.Inclusion Criteria
My cancer has a KRAS G12C mutation.
I've had 1-2 treatments for advanced lung cancer.
I am 18 years old or older.
+8 more
Exclusion Criteria
I haven't had any cancer treatments in the last 4 weeks.
I've needed treatment for a skin condition in the last year.
I haven't taken strong CYP3A4 affecting drugs in the last 14 days.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive avutometinib (VS-6766) in combination with sotorasib with or without defactinib to determine the recommended phase 2 dose (RP2D) and assess efficacy
16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Up to 5 years
Participant Groups
The trial tests avutometinib combined with sotorasib on patients with G12C Non-Small Cell Lung Cancer. It's looking at how safe and effective this combo is for those who've had previous treatment with a G12C inhibitor and those who haven't.
6Treatment groups
Experimental Treatment
Group I: avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor naiveExperimental Treatment1 Intervention
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
Group II: avutometinib (VS-6766)+sotorasib+defactinib - KRAS G12C inhibitor exposedExperimental Treatment1 Intervention
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients
Group III: avutometinib (VS-6766)+sotorasib+defactinibExperimental Treatment1 Intervention
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients
Group IV: avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor naïveExperimental Treatment1 Intervention
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor naïve patients
Group V: avutometinib (VS-6766)+sotorasib - KRAS G12C inhibitor exposedExperimental Treatment1 Intervention
To determine the efficacy of the RP2D identified from Part A in KRAS G12C inhibitor exposed patients
Group VI: avutometinib (VS-6766)+sotorasibExperimental Treatment1 Intervention
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients
Avutometinib (VS-6766) is already approved in United States for the following indications:
🇺🇸 Approved in United States as Avutometinib for:
- Recurrent low-grade serous ovarian cancer (Breakthrough Therapy Designation)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dana Farber Cancer InstituteBoston, MA
MedStar Washington Hospital Center, MedStar Georgetown Cancer Institute,Washington, United States
Alliance Cancer Specialists,Horsham, PA
Texas Oncology - Fort Worth Cancer CenterFort Worth, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Verastem, Inc.Lead Sponsor
AmgenIndustry Sponsor
References
Sotorasib: First Approval. [2022]Sotorasib (LUMAKRAS™) is a RAS GTPase family inhibitor being developed by Amgen for the treatment of solid tumours with KRAS mutations, including non-small cell lung cancer (NSCLC) and colorectal cancer. In May 2021, sotorasib was granted accelerated approval by the US FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This article summarizes the milestones in the development of sotorasib leading to this first approval for KRAS G12C-mutated NSCLC.
Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor. By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA. A clinically relevant objective response rate was observed in patients with KRAS G12C mutation-positive NSCLC during the primary analysis and in an updated analysis of the phase I/II CodeBreaK 100 trial. Furthermore, a clinically relevant response duration was reported in updated analyses of the trial. Sotorasib has a manageable tolerability profile, with permitted dose modifications to manage toxicity. In summary, sotorasib is a promising KRASG12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.
FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. [2022]On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% [95% confidence interval (CI), 28-45]. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.
Sotorasib as First-Line Treatment for Advanced KRAS G12C-Mutated Non-Small Cell Lung Carcinoma: A Case Report. [2023]Mutations in the KRAS gene are the most common gain-of-function mutations found in lung adenocarcinomas. The most common mutation, KRAS G12C, is present in 13% of lung adenocarcinomas. Sotorasib (AMG-510) is an irreversible small molecule inhibitor targeting KRAS G12C. In preclinical studies, treatment with sotorasib led to the regression of KRAS G12C-mutated tumors, and clinical efficacy in NSCLC was demonstrated in clinical trials. In May 2021, sotorasib received US FDA approval for treatment of KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. In this report, we present a case with metastatic, KRAS G12C-mutated NSCLC who responded favorably to sotorasib as first-line therapy. The efficacy of sotorasib as first-line treatment in this patient was remarkable, which supports further study of sotorasib as first-line therapy for KRAS G12C-mutated NSCLC, especially in fragile patients with comorbidities.
An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. [2022]Label="INTRODUCTION" NlmCategory="UNASSIGNED">Improving the clinical outcomes of patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), the majority of whom are current or former smokers, has been a barrier to improving population-level outcomes in NSCLC. Novel and effective KRASG12C inhibitors are emerging, and sotorasib is the first member of that class to achieve commercial availability.
Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. [2023]Label="OBJECTIVE" NlmCategory="UNASSIGNED">To evaluate the safety and efficacy of the novel KRAS-targeting agents, sotorasib and adagrasib, in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Clinical and Genomic Features of Response and Toxicity to Sotorasib in a Real-World Cohort of Patients With Advanced KRAS G12C-Mutant Non-Small Cell Lung Cancer. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">With the recent approval of the KRAS G12C inhibitor sotorasib for patients with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), there is a new need to identify factors associated with activity and toxicity among patients treated in routine practice.
Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022]Label="BACKGROUND">Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).