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

NCT ID: NCT05673187

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-12
• Study Completion Date: 2026-03-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

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

Group Type: EXPERIMENTAL

Adagrasib

Intervention Type: DRUG

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

Interventions

Adagrasib

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed stage IV NSCLC.

2. KRASG12C-mutation by local testing (by tissue or ctDNA).

3. 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).

4. Life expectancy ≥12 weeks.

5. Measurable disease according to RECIST v1.1.

6. Age ≥18 years with ECOG PS 2 (cohort 1), or age ≥70 years with ECOG PS 0-1 (cohort 2).

7. Adequate haematological, renal and liver function

8. Men and women of childbearing potential must agree to use use highly effective contraceptive methods.

9. 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.

10. 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.

Exclusion Criteria

1. Prior investigational therapy within 28 days or at least 5 half-lives before enrolment.

2. Prior treatment with an agent targeting KRASG12C.

3. 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.

4. History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.

5. 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.

6. History of stroke or transient ischemic attack within 6 months prior to enrolment.

7. 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.

8. Known human immunodeficiency virus (HIV) infection.

9. Acute or chronic hepatitis B or C infection.

10. Women who are pregnant or in the period of lactation.

11. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.

12. Judgement 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jarushka Naidoo

Role: STUDY_CHAIR

Beaumont RCSI Cancer Centre, Beaumont Hospital

Locations

Instiute Jules Bordet

Brussels, , Belgium

Centre Hospitalier d'Avignon

Avignon, , France

Caen - CHU

Caen, , France

Le Mans - CHG

Le Mans, , France

Hôpital de Marseille

Marseille, , France

Beaumont Hospital

Dublin, , Ireland

St James's Hospital

Dublin, , Ireland

University Hospital Limerick

Limerick, , Ireland

University Hospital Waterford

Waterford, , Ireland

Fondazione IRCCS Policlinico S. Matteo

Pavia, , Italy

Santa Maria della Misericordia Hospital

Perugia, , Italy

Istituto Nazionale Tumori "Regina Elena"

Rome, , Italy

AULSS2 Marca Trevigiana Treviso

Treviso, , Italy

Complejo Hospitalario Universitario a Coruña

A Coruña, , Spain

Alicante University Hospital

Alicante, , Spain

ICO Badalona - Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital de Basurto

Bilbao, , Spain

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

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Hospital General Universitario de Valencia (University Hospital Valencia)

Valencia, , Spain

Christie NHS Manchester

Manchester, , United Kingdom

Countries

Belgium; France; Ireland; Italy; Spain; United Kingdom

Other Identifiers

2022-002736-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ETOP 22-22

Identifier Type: -

Identifier Source: org_study_id