Phase 2 Study of Adagrasib Monotherapy and in Combination With Pembrolizumab and Phase 3 Study of Adagrasib in Combination with Pembrolizumab versus Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mirati Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

17 Mar 2021 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Mirati Therapeutics, Inc.

External identifiers

EU CT number

2023-508922-83-00

EudraCT number

2020-003101-58

ClinicalTrials.gov

NCT04613596

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Safety, Pharmacogenetic, Pharmacogenomic, Therapy

Phase 2: To evaluate the efficacy of adagrasib monotherapy and in combination with Pembrolizumab administered in the first-line treatment setting to patients having NSCLC with KRAS G12C mutation.
Phase 3: To compare the efficacy of adagrasib in combination with pembrolizumab versus pembrolizumab alone in first-line NSCLC with KRAS G12C mutation and PD-L1 ≥ 50%.

Secondary objectives 7

1. Phase 2: • To characterize the safety and tolerability of the monotherapy and the combination regimen in the selected population.
2. Phase 2: • To evaluate secondary efficacy endpoints using monotherapy and the combination regimen in the selected population.
3. Phase 2: • To evaluate the pharmacokinetics (PK) of adagrasib administered as monotherapy and in combination with pembrolizumab.
4. Phase 3: • To evaluate secondary efficacy endpoints in the study population
5. Phase 3: • To evaluate the safety and tolerability in the study population
6. Phase 3: • To evaluate the pharmacokinetics (PK) of adagrasib administered in the study population
7. Phase 3: • To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population

Conditions and MedDRA coding

Advanced Non-Small Cell Lung Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Phase 2: Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation and known PD-L1 TPS score and presence of measurable disease per RECIST v1.1.
2. Phase 3: Histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC (squamous or nonsquamous) with KRAS G12C mutation and PD-L1 ≥ 50% confirmed using Sponsor-approved testing (refer to laboratory manual for current list of Sponsor-approved tests).
3. Phase 2 and 3: Presence of evaluable or measurable disease per RECIST version 1.1.
4. Phase 3: CNS Inclusion–- Based on screening brain imaging, patients must have one of the following: 1. No evidence of brain metastases 2. Untreated asymptomatic brain metastases < 2.0 cm not needing immediate local therapy 3. Previously treated brain metastases not needing immediate local therapy .
5. Phase 2 and Phase 3: Not a candidate for definitive therapy (eg, chemoradiation for locally advanced disease).
6. Phase 3: A representative tumor specimen (primary or metastatic and newly obtained or archival sample must be available to be submitted to the Sponsor during screening or within 30 days of randomization.

Exclusion criteria 4

1. Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune CIT, or a therapy targeting KRAS G12C mutation (e.g., sotorasib)
2. Phase 2 and Phase 3: Radiation to the lung > 30 Gy within 6 months prior to the first dose of study treatment.
3. Phase 2: Active brain metastases
4. Phase 3: Patients with known central nervous system (CNS) lesions must not have any of the following: 1. Any untreated or symptomatic brain lesions > 2.0 cm in size 2. Any brainstem lesions 3. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of > 10 mg of prednisone (or equivalent) prior to randomization. 4. Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain lesions notwithstanding CNS-directed therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 2: Obejective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Investigator
2. Phase 3: Dual primary endpoints: 1. PFS (RECIST 1.1) by BICR 2. OS

Secondary endpoints 7

1. Phase 2: 1. Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities
2. Phase 2: 2. Duration of Response (DOR), Progression - Free Survival (PFS), 1-Year Survival rate, Overall Survival (OS)
3. Phase 2: 3. Pharmacokinetics (PK) Blood plasma adagrasib and potential metabolite concentrations
4. Phase 3: 1. PFS (RECIST v1.1) by Investigator - OR (RECIST v1.1) by Investigator and BICR - DOR (RECIST v1.1) by Investigator and BICR1
5. Phase 3: 2. Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of AEs, laboratory abnormalities, and number of patients discontinuing study treatment due to an AE
6. Phase 3: 3. Population PK parameters of adagrasib
7. Phase 3: 4. Patient-reported outcome (PRO) to measure quality of life

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mirati Therapeutics Inc.

Sponsor organisation

Mirati Therapeutics Inc.

Address

Route 206, Province Line Road Province Line Road

City

Princeton

Postcode

08543

Country

United States

Scientific contact point

Organisation

Mirati Therapeutics Inc.

Contact name

GSM-CT Representative

Public contact point

Organisation

Mirati Therapeutics Inc.

Contact name

GSM-CT Representative

Third parties 10

Locations

19 EU/EEA countries · 146 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 338 files

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

Application history

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