Platform study of JDQ443 in combinations in patients with advanced solid tumors harboring the KRAS G12C 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

8 May 2023 → ongoing

Decision date (initial)

2023-12-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-506716-41-00

EudraCT number

2021-006196-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Therapy, Safety, Pharmacokinetic

Dose escalation
To characterize safety and tolerability of each treatment arm tested and
identify the recommended doses and regimens for future studies.
Phase II
To assess the anti-tumor activity of each treatment arm.

Secondary objectives 5

1. Dose escalation To assess the preliminary anti-tumor activity of each treatment arm
2. Dose escalation To characterize the PK of JDQ443 and corresponding combination
3. Phase II To assess the preliminary anti-tumor activity of each treatment arm
4. Phase II To assess safety and tolerability of each treatment arm tested
5. Phase II To characterize the PK of JDQ443 and corresponding combination partner(s), as applicable, for each treatment arm

Conditions and MedDRA coding

Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Dose Escalation: Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.
2. Phase II: Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
3. Phase II: Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.
4. All patients: ECOG performance status of 0 or 1.
5. All patients: Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines.

Exclusion criteria 5

1. Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations.
2. Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of groups in Phase II.
3. Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease
4. Clinically significant cardiac disease or risk factors at screening
5. Insufficient bone marrow, hepatic or renal function at screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.
2. Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
3. Dose escalation: Frequency of dose interruptions and reductions, by treatment
4. Dose Escalation: Dose intensity by treatment
5. Phase II: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1

Secondary endpoints 8

1. Dose escalation and Phase II: ORR by local review per RECIST 1.1
2. Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1
3. Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1
4. Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1
5. Phase II: DCR by BIRC per RECIST 1.1
6. Phase II: DoR by BIRC per RECIST 1.1
7. Phase II: PFS by BIRC per RECIST 1.1
8. Phase II: Overall survival (OS)

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

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 13

Locations

5 EU/EEA countries · 9 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 4 · 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 54 files

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

Application history

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