Clinical trial NCT06068153: AMG510 (sotorasib) Plus Lenvatinib As Second-line Treatment in Patients with KRASG12C Mutant, Metastatic NSCLC
Official title: A Multicentre, Single-arm Phase II Trial of Sotorasib Plus Lenvatinib, As Second-line Treatment in Patients with KRASG12C-mutant, Metastatic NSCLC
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Non Small Cell Lung Cancer
KRAS G12C
Keywords: Metastatic NSCLC
KRAS G12C
Sotorasib
Lenvatinib
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Amgen
name: Eisai Inc.
First posted: 2023-10-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: From date of enrolment until 18 weeks post-enrolment.
Secondary outcomes:
measure: Progression-free survival per RECIST v1.1
timeFrame: From the date of enrolment until last tumour assessment (approximately 22 months after the enrolment of the first patient)
measure: Disease control rate per RECIST v1.1
timeFrame: From date of enrolment until 18 weeks post-enrolment.
measure: Overall survival
timeFrame: From the date of enrolment until death from any cause (up to 22 months after the enrolment of the first patient)
measure: Duration of response
timeFrame: From the date of enrolment until last tumour assessment or death from any cause (approximately 22 months after the enrolment of the first patient)
measure: Adverse events according to CTCAE v5.0
timeFrame: [Time Frame: From the date of enrolment until last patient last visit (approximately 22 months after enrolment of the first patient)]
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck / UK für Innere Medizin V
city: Munich
country: Germany
facility: University Hospital of Munich (LMU), Department of Medicine V (Pneumology/Thoracic Oncology)
city: Alicante
country: Spain
facility: Alicante University Dr Balmis Hospital ISABIAL
city: Badalona
country: Spain
facility: Ico Badalona - Hospital Germans Trias I Pujol
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santa Cruz De Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Toledo
country: Spain
facility: Hospital Universitario de Toledo
city: Valencia
country: Spain
facility: Hospital Universitario Y Politécnico La Fe
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Fribourg
country: Switzerland
facility: HFR Fribourg
city: Geneva
country: Switzerland
facility: HUG
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
Study officials:
affiliation: Département d'Oncologie Hôpitaux Universitaires de Genève
name: Alfredo Addeo
role: STUDY_CHAIR
affiliation: Royal Marsden NHS Foundation Trust
name: Sanjay Popat
role: STUDY_CHAIR
References: