Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status

NCT05673187 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ETOP 22-222022-002736-31
• Study Type: interventional
• Target: 68
• Locations: 6 countries
• Sites: 22

Brief Summary

ADEPPT is an international, multicentre, single-arm phase II trial. The protocol treatment consists of adagrasib, which is administered at a dose of 600 mg orally, twice daily until progression or unacceptable toxicity.The primary objective of this trial is to assess the clinical efficacy of adagrasib treatment, in terms of objective response, in patients with KRASG12C-mutant NSCLC, including the elderly (≥70 years) or patients with poor performance status (ECOG PS=2).

Conditions

NSCLC Stage IV; KRAS P.G12C

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) per RECIST v1.1, assessed at 12 weeks.

  The primary objective of this trial is to assess the clinical efficacy of adagrasib treatment, in terms of objective response as defined as the rate of patients achieving a best overall response \[complete response (CR) or partial response (PR)\] according to RECIST v1.1

  From date of enrolment until 12 weeks post-enrolment

Secondary Outcomes (14)

• Durable clinical benefit

  From date of enrolment until at least the 24-week assessment.

• Time-to-progression (TTP)

  From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)

• Progression-free survival (PFS)

  From the date of enrolment until last tumour assessment (approximately 20-26 months after enrolment of the first patient)

• Overall survival (OS)

  From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)

• Safety and tolerability

  From the date of enrolment until last patient last visit (approximately 20-26 months after enrolment of the first patient)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Adagrasib to be administered at a dose of 600 mg orally, twice daily until progression or unacceptable toxicity.

Drug: Adagrasib

Interventions

Adagrasib DRUG

Adagrasib is administered at a dose of 600 mg orally, twice 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:

• Histologically or cytologically confirmed stage IV NSCLC.
• KRASG12C-mutation by local testing (by tissue or ctDNA).
• Prior treatment with at least one line of systemic therapy for NSCLC (e.g., platinum-based doublet chemotherapy and/or immune-checkpoint inhibition or both).
• Life expectancy ≥12 weeks.
• Measurable disease according to RECIST v1.1.
• Age ≥18 years with ECOG PS 2 (cohort 1), or age ≥70 years with ECOG PS 0-1 (cohort 2).
• Adequate haematological, renal and liver function
• Men and women of childbearing potential must agree to use use highly effective contraceptive methods.
• Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum beta HCG pregnancy test within 5 weeks before enrolment. Pregnancy test must be repeated within 7 days before the first dose of adagrasib treatment.Ability to comply with the trial protocol, in the investigator's judgment.
• Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention, including the submission of mandatory biomaterial.

You may not qualify if:

• Prior investigational therapy within 28 days or at least 5 half-lives before enrolment.
• Prior treatment with an agent targeting KRASG12C.
• Leptomeningeal disease or untreated brain metastases.
• Patient should be neurologically stable for at least 2 weeks before enrolment, without the need for corticosteroids, except for prednisone (or its equivalent) at a dose of ≤10 mg daily.
• For patients with definitively treated brain metastases, a time period of minimum of 2 weeks must have elapsed from the last day of radiotherapy.
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
• Any of the following cardiac abnormalities:
• Unstable angina pectoris or myocardial infarction within 6 months prior to enrolment.
• Symptomatic or uncontrolled atrial fibrillation within 6 months prior to enrolment.
• Congestive heart failure ≥NYHA Class 3 within 6 months prior to enrolment.
• Prolonged QTc interval \>480 ms or family or medical history of congenital Long QT Syndrome.
• History of stroke or transient ischemic attack within 6 months prior to enrolment.
• Ongoing need for treatment with concomitant medication with any of the following characteristics: known risk of Torsades de Pointes; substrate of CYP3A with narrow therapeutic index; strong inducer of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors that cannot be switched to alternative treatment prior to enrolment.
• Known human immunodeficiency virus (HIV) infection.
• Acute or chronic hepatitis B or C infection.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (22)

Instiute Jules Bordet

Brussels, Belgium

Location

Centre Hospitalier d'Avignon

Avignon, France

Location

Caen - CHU

Caen, France

Location

Le Mans - CHG

Le Mans, France

Location

Hôpital de Marseille

Marseille, France

Location

Beaumont Hospital

Dublin, Ireland

Location

St James's Hospital

Dublin, Ireland

Location

University Hospital Limerick

Limerick, Ireland

Location

University Hospital Waterford

Waterford, Ireland

Location

Fondazione IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Santa Maria della Misericordia Hospital

Perugia, Italy

Location

Istituto Nazionale Tumori "Regina Elena"

Rome, Italy

Location

AULSS2 Marca Trevigiana Treviso

Treviso, Italy

Location

Complejo Hospitalario Universitario a Coruña

A Coruña, Spain

Location

Alicante University Hospital

Alicante, Spain

Location

ICO Badalona - Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

ICO Bellvitge -H. Duran i Reynals / H. Bellvitge

L'Hospitalet de Llobregat, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital General Universitario de Valencia (University Hospital Valencia)

Valencia, Spain

Location

Christie NHS Manchester

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

adagrasib

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

• Jarushka Naidoo

  Beaumont RCSI Cancer Centre, Beaumont Hospital

  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: November 14, 2022
• First Posted: January 6, 2023
• Study Start: June 12, 2023
• Primary Completion: July 28, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

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

Locations

FR (4); IT (4); GB (1); ES (8); IE (4); BE (1)