AMG510 (Sotorasib) Plus Lenvatinib as Second-line Treatment in Patients With KRASG12C Mutant, Metastatic NSCLC

• Status: Withdrawn
• Trial end date: 2026-12-30
• Target enrollment: 0
• Participant gender: All

Summary

AMBER is a multicentre, single-arm phase II trial. The protocol treatment consists of of sotorasib plus lenvatinib, as a second-line treatment. The primary objective of the trial is to evaluate the clinical efficacy of sotorasib plus lenvatinib, in terms of objective response rate, for patients with KRASG12C-mutant, metastatic NSCLC.

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

Details

• Lead Sponsor: ETOP IBCSG Partners Foundation
• Collaborators: Amgen; Eisai Inc.
• Treatments: Lenvatinib; Sotorasib

Criteria

Inclusion Criteria:

• Pathologically documented metastatic NSCLC.

• Documented disease progression on prior treatment. Prior treatment must have included platinum-based doublet chemotherapy and immune-checkpoint inhibition.

• KRASG12C-mutation (identified through local molecular testing, using a validated test).

• Measurable disease per RECIST v1.1 criteria.

• Age ≥18 years.

• ECOG Performance Status of 0-1.

• Life expectancy of >3 months.

• Ability to swallow oral medications and willing to complete a treatment diary.

• Adequate haematological function.

• Adequate renal function.

• Adequate liver function.

• Men and women of childbearing potential must use highly effective contraception.

• Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 5 weeks before enrolment. Pregnancy test must be repeated within 3 days before the first dose of protocol treatment.

• Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Exclusion Criteria:

• Active brain metastases E.g., untreated brain lesions (new or progressing) and/or symptomatic brain lesions (symptoms as determined by the investigator).

Patients who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks (or stereotactic radiosurgery ending at least 2 weeks) prior to enrolment are eligible if they meet all of the following criteria:

• Residual neurological symptoms are only of grade ≤2

• On stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable.

• History or presence of haematological malignancies. Exception: curatively treated haematological malignancies with no disease evidence in the last 2 years.

• History of (non-infectious) pneumonitis that required steroids or evidence of ILD/pneumonitis.

• Active hepatitis B and C and uncontrolled HIV.

• Uncontrolled blood pressure (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg) in spite of an optimised regimen of antihypertensive medication.

• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, long QT syndrome (LQTS), unstable angina, myocardial infarction or stroke within 6 months before enrolment, or cardiac arrhythmia requiring medical treatment at screening

• Bleeding or thrombotic disorders or patients at risk for severe haemorrhage. The degree of tumour invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe haemorrhage associated with tumour shrinkage/necrosis following lenvatinib therapy.

• Current or recent (within 10 days of enrolment) use of aspirin (>325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, or clostazol.

• Electrolyte abnormalities that have not been corrected.

• Proteinuria on urine dipstick testing >1+, unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <2 g/24 hours.

• History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to inclusion.

• Unresolved toxicities from previous lines of anti-cancer treatment regimens and/or (with the exception of alopecia) complications from major surgery prior to enrolment.

• Previous treatment with KRAS- and/or VEGF/R inhibitors.

• Hypersensitivity to sotorasib or lenvatinib.

• Women who are pregnant or breastfeeding or who are planning to become pregnant or breastfeed.

• Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and for 7 days after the last dose of sotorasib and until 30 days after the last dose of lenvatinib.

• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.