ETOP 22-22 ADEPPT: A study of adagrasib for patients with KRASG12C-mutant non-small cell lung cancer (NSCLC), who are elderly or who are unwell because of their lung cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

26 Apr 2023 → ongoing

Decision date (initial)

2024-03-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Mirati Therapeutics, Inc.

External identifiers

EU CT number

2023-510463-35-00

EudraCT number

2022-002736-31

ClinicalTrials.gov

NCT05673187

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

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).

Secondary objectives 1

1. The secondary objectives refer to the evaluation of measures of clinical efficacy including durable clinical benefit (DCB), time-to-progression (TTP), progression-free survival (PFS), overall survival (OS), overall safety and patient-related outcomes.

Conditions and MedDRA coding

Patients with KRASG12C-mutant NSCLC, including patients aged ≥18 years with poor performance status (ECOG PS=2) Cohort 1 or elderly (≥70 years) (ECOG PS=0-1) Cohort 2

Study design 7 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Most important inclusion criterias:- 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 - Negative pregnancy test for patients of childbearing potential - Ability to comply with the trial protocol, in the investigator's judgment. -Written informed consent for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial.

Exclusion criteria 1

1. -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 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. Note that the following are permitted: a. Patients treated for hepatitis C (HCV) with no detectable viral load at screening; b. Patients treated for HIV with no detectable viral load for at least 1 month prior to enrolment; and c. Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA <2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBcAg-positive]) -Women who are pregnant or in the period of lactation -Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study -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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 1

1. - Durable clinical benefit (DCB) - Time to progression (TTP) - Progression-free Survival (PFS) - Overall Survival (OS) - Safety - Patient-related outcomes

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Third parties 3

Locations

5 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications