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

NCT06068153 | Withdrawn Phase 2 DMC

• 1 other identifier: ETOP 24-22
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 15

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.

Conditions

Metastatic Non Small Cell Lung Cancer; KRAS G12C

Keywords

Metastatic NSCLC; KRAS G12C; Sotorasib; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the rate of patients, among all enrolled patients, achieving a best overall response \[complete response (CR) or partial response (PR)\] according to RECIST v1.1, investigator assessed, by 18 weeks post-enrolment.

  From date of enrolment until 18 weeks post-enrolment.

Secondary Outcomes (5)

• Progression-free survival per RECIST v1.1

  From the date of enrolment until last tumour assessment (approximately 22 months after the enrolment of the first patient)

• Disease control rate per RECIST v1.1

  From date of enrolment until 18 weeks post-enrolment.

• Overall survival

  From the date of enrolment until death from any cause (up to 22 months after the enrolment of the first patient)

• Duration of response

  From the date of enrolment until last tumour assessment or death from any cause (approximately 22 months after the enrolment of the first patient)

• Adverse events according to CTCAE v5.0

  [Time Frame: From the date of enrolment until last patient last visit (approximately 22 months after enrolment of the first patient)]

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Sotorasib + Lenvatinib

Drug: Sotorasib; Drug: Lenvatinib

Interventions

Sotorasib DRUG

Sotorasib is administered at a dose of 960 mg (8x 120 mg) orally, once daily until progression or unacceptable toxicity.

Treatment Arm

Lenvatinib DRUG

Lenvatinib is administered at a dose of 20 mg orally (2x 10 mg), once daily until progression or unacceptable toxicity.

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Amgen: collaborator
• Eisai Inc.: collaborator

Study Sites (15)

Medical University of Innsbruck / UK für Innere Medizin V

Innsbruck, Austria

Location

University Hospital of Munich (LMU), Department of Medicine V (Pneumology/Thoracic Oncology)

Munich, Germany

Location

Alicante University Dr Balmis Hospital ISABIAL

Alicante, Spain

Location

Ico Badalona - Hospital Germans Trias I Pujol

Badalona, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, Spain

Location

Hospital Universitario de Toledo

Toledo, Spain

Location

Hospital Universitario Y Politécnico La Fe

Valencia, Spain

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, Switzerland

Location

Kantonsspital Graubünden

Chur, Switzerland

Location

HFR Fribourg

Fribourg, Switzerland

Location

HUG

Geneva, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib; lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Alfredo Addeo

  Département d'Oncologie Hôpitaux Universitaires de Genève

  STUDY CHAIR

• Sanjay Popat

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2023
• First Posted: October 5, 2023
• Study Start: March 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

AU (1); ES (8); CH (5); DE (1)