AMG510 (sotorasib) Plus Lenvatinib As Second-line Treatment in Patients with KRASG12C Mutant, Metastatic NSCLC (AMBER)

ETOP IBCSG Partners Foundation

Status and phase

Withdrawn

Phase 2

Conditions

KRAS G12C

Metastatic Non Small Cell Lung Cancer

Treatments

Drug: Sotorasib

Drug: Lenvatinib

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT06068153

ETOP 24-22

Details and patient eligibility

About

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.