Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments (KontRASt-R)

Novartis

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer; Advanced Solid Tumors Harboring the KRAS G12C Mutation

Treatments: Biological: cetuximab; Drug: Opnurasib; Drug: TNO155; Biological: tislelizumab; Drug: trametinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT07468071

CJDQ443B12105B

2025-523537-26-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to allow continued access to opnurasib (JDQ443) to participants who are benefitting from treatment with opnurasib as a single agent or in combination with other study treatments in pre-defined Novartis-sponsored opnurasib studies and to continue to assess safety in these participants.

Full description

Screening occurs on the same day as the parent study's End of Treatment visit, with informed consent and eligibility confirmation required before enrollment. Eligible participants start treatment within seven days and return for scheduled visits for drug resupply, safety monitoring, and confirmation of clinical benefit. Sites are expected to follow their local practice regarding the method and frequency of the assessments used to assess clinical benefit for the patient. Treatment continues until disease progression or other discontinuation criteria, and safety follow-up lasts 30-150 days depending on the last drug received. The study will remain open for up to three years from first participant visit or until all participants discontinue.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participant is currently enrolled in a pre-defined Novartis-sponsored study and is receiving opnurasib as single agent or in combination with other study treatment.
• Participant has received at least 6 cycles of opnurasib in a parent study.
• Participant is currently deriving clinical benefit from the study treatment, as determined by the Investigator.

Key Exclusion Criteria:

• Participant has been permanently discontinued from opnurasib in the parent protocol for any reason other than enrollment in the CJDQ443B12105B study.
• Participant is not willing to comply with the contraception requirements outlined in the exclusion criteria of the parent protocol.
• Participant currently has unresolved toxicities for which opnurasib dosing has been interrupted in the parent study.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 5 patient groups

Group 1: opnurasib single agent

Experimental group

Description:

Eligible participants will receive the same starting dose and regimen of opnurasib as the last dose and regimen administered before completing the parent protocol at the time of transition to the rollover study.

Treatment:

Drug: Opnurasib

Group 2: opnurasib + TNO155

Experimental group

Description:

Eligible participants will receive the same starting dose and regimen of opnurasib and any applicable combination drug as the last dose and regimen administered before completing the parent protocol at the time of transition to the rollover study.

Treatment:

Drug: TNO155

Drug: Opnurasib

Group 3: opnurasib + trametinib

Experimental group

Description:

Eligible participants will receive the same starting dose and regimen of opnurasib and any applicable combination drug as the last dose and regimen administered before completing the parent protocol at the time of transition to the rollover study.

Treatment:

Drug: trametinib

Drug: Opnurasib

Group 4: opnurasib + cetuximab

Experimental group

Description:

Eligible participants will receive the same starting dose and regimen of opnurasib and any applicable combination drug as the last dose and regimen administered before completing the parent protocol at the time of transition to the rollover study.

Treatment:

Biological: cetuximab

Drug: Opnurasib

Group 5: opnurasib + tislelizumab

Experimental group

Description:

Eligible participants will receive the same starting dose and regimen of opnurasib and any applicable combination drug as the last dose and regimen administered before completing the parent protocol at the time of transition to the rollover study.

Treatment:

Biological: tislelizumab

Drug: Opnurasib