Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung CancerPhase 1/2KontRASt-RNCT07468071
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
A Phase 1/2 study testing Opnurasib, TNO155 and trametinib in people with Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer and Advanced Solid Tumors Harboring the KRAS G12C Mutation, run by Novartis Pharmaceuticals at 21 sites in 10 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer, Advanced Solid Tumors Harboring the KRAS G12C Mutation
- What is being tested?
- Opnurasib, TNO155 and trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 21 sitesin 10 countries
- Study dates
- 8 Jun 2026to 11 Sep 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Participants currently receiving treatment in one of the KontRASt studies, including those who have not experienced disease progression or who are continuing treatment beyond initial disease progression, may be eligible to enroll in the rollover study if, in the Investigator's judgment, they are expected to continue deriving clinical benefit from treatment with opnurasib (alone or in combination). Clinical benefit, as assessed by the Investigator, may be reflected by delayed disease progression, improvement in disease-related symptoms, improvement in overall quality of life, or a combination of these factors.
Who cannot join
- 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.
- Participant has known actionable mutations, such as EGFR-sensitizing mutation, ALK rearrangement, or others, identified during the participation in the parent trial for which there are available treatment options.
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
21 sites in 10 countries.
21 sites in 10 countries
Spain4 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Valencia, 46010
France3 sites
Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Saint-Herblain, 44805
Novartis Investigative Site
Villejuif, 94800
Italy3 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Roma, RM, 00128
Belgium2 sites
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Sint-Niklaas, Oost Vlaanderen, 9100
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H4A 3J1
Novartis Investigative Site
Sherbrooke, Quebec, J1H 5N4
China2 sites
Novartis Investigative Site
Changsha, Hunan, 410013
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Japan2 sites
Novartis Investigative Site
Kashiwa, Chiba, 2778577
Novartis Investigative Site
Koto Ku, Tokyo, 1358550
About this study
Official title: KontRASt-R: An Open-label, Multi-center, Rollover Study for Participants Who Have Been Previously Enrolled Into a Novartis-sponsored Opnurasib (JDQ443) Study and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments
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.
Read the detailed 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.
- Conditions
- Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer, Advanced Solid Tumors Harboring the KRAS G12C Mutation
- Being tested
- Opnurasib, TNO155, trametinib, cetuximab, tislelizumab
- Keywords
- KRAS G12C, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), advanced solid tumors, opnurasib (JDQ443), TNO155, trametinib (TMT212), cetuximab, tislelizumab (VDT482)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OpnurasibDrug
Also called JDQ443
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.
TNO155Drug
Eligible participants will receive the same starting dose and regimen of 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.
trametinibDrug
Also called TMT212
Eligible participants will receive the same starting dose and regimen of 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.
cetuximabBiological
Eligible participants will receive the same starting dose and regimen of 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.
tislelizumabBiological
Also called VDT482
Eligible participants will receive the same starting dose and regimen of 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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: opnurasib single agent | Experimental | 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. Receives: Drug: Opnurasib |
| Group 2: opnurasib + TNO155 | Experimental | 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. Receives: Drug: Opnurasib; Drug: TNO155 |
| Group 3: opnurasib + trametinib | Experimental | 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. Receives: Drug: Opnurasib; Drug: trametinib |
| Group 4: opnurasib + cetuximab | Experimental | 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. Receives: Drug: Opnurasib; Biological: cetuximab |
| Group 5: opnurasib + tislelizumab | Experimental | 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. Receives: Drug: Opnurasib; Biological: tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants receiving opnurasib as single agent or in combination with other study treatments
The number of participants enrolled and receiving opnurasib as single agent or in combination with other study treatments under the rollover study, will be summarized by treatment arm.
Measured: Assessed up to approximately 3 years
Duration of exposure to study treatment
The duration of exposure in months to opnurasib and the combination partner will be summarized by means of descriptive statistics using the SAS.
Measured: Assessed up to approximately 3 years
Secondary outcomes (2)
Incidence rate of Adverse Events (AEs)
The distribution of adverse events will be evaluated by analyzing the frequencies of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs).
In this study, TEAEs are defined as AEs with an onset date after the start of the treatment period, or events that were present before the treatment period but subsequently increased in severity, changed from not suspected to suspected of being related to study treatment, or evolved into SAEs after the start of the treatment period.
The safety follow-up period will extend from the first administration of study treatment until:
- 30 days after the last dose for participants receiving opnurasib as monotherapy or in combination with TNO155 or trametinib,
- 60 days after the last dose for participants receiving opnurasib in combination with cetuximab, and
- 150 days after the last dose for participants receiving opnurasib in combination with tislelizumab.
Measured: Assessed up to approximately 3 years
Number of participants with dose adjustments
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Measured: Assessed up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2026
- Study start8 Jun 2026
- Primary completion11 Jun 2029 (estimated)
- Study completion11 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07468071
- Sponsor's protocol ID
- CJDQ443B12105B
- Other IDs
- 2025-523537-26-00, 2025
- Acronym
- KontRASt-R
- Status last verified
- Oct 2026
- First submitted
- 9 Mar 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com