Study of efficacy and safety of JDQ443 single-agent as first-line treatment for patients with locally advanced or metastatic KRAS G12C- mutated nonsmall cell lung cancer with a PD-L1 expression < 1% or a PD-L1 expression ≥ 1% and an STK11 co-mutation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Dec 2022 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-511708-18-00

EudraCT number

2022-001088-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation and a PD-L1 expression < 1%, regardless of STK11 mutation status (cohort A).

Secondary objectives 1

1. To assess the antitumor activity of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥1% and an STK11 co-mutation (cohort B).

Conditions and MedDRA coding

Locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer with a PD-L1 expression < 1% or a PD-L1 expression ≥ 1% and an STK11 co-mutation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation or surgical resection with curative intent) or metastatic (stage IV) NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or locally advanced disease are accepted if the time between therapy completion and enrollment is > 12 months.
2. Presence of a KRAS G12C mutation (all participants) and: • Cohort A: PD-L1 expression < 1%, regardless of STK11 mutation status • Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation
3. At least one measurable lesion per RECIST 1.1.
4. ECOG performance status ≤ 1.
5. Participants capable of swallowing study medication.

Exclusion criteria 5

1. Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other known druggable alterations will be excluded, if required by local guidelines
2. Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic NSCLC.
3. A medical condition that results in increased photosensitivity (i.e., solar urticaria, lupus erythematosus, etc.).
4. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
5. Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR), defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the investigator.

Secondary endpoints 3

1. ORR per RECIST 1.1 as determined by the investigator
2. Type, frequency and severity of adverse events, changes in laboratory values, vital signs, electrocardiograms (ECGs).
3. Concentration of JDQ443 in plasma and derived PK parameters, as appropriate

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 15

Locations

10 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 9 · Art. 38 CTR

Results and documents

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

Documents 103 files

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

Application history

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