Locally Advanced or Metastatic KRAS G12C-mutated Non-small Cell Lung Cancer, Advanced Solid Tumors Harboring the KRAS G12C Mutation
Conditions
Keywords
KRAS G12C, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), advanced solid tumors, opnurasib (JDQ443), TNO155, trametinib (TMT212), cetuximab, tislelizumab (VDT482)
Brief 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.
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.
Interventions
DRUGOpnurasib
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.
DRUGTNO155
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.
DRUGtrametinib
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.
BIOLOGICALcetuximab
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.
BIOLOGICALtislelizumab
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants receiving opnurasib as single agent or in combination with other study treatments | Assessed up to approximately 3 years | 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. |
| Duration of exposure to study treatment | Assessed up to approximately 3 years | The duration of exposure in months to opnurasib and the combination partner will be summarized by means of descriptive statistics using the SAS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate of Adverse Events (AEs) | Assessed up to approximately 3 years | 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: 1. 30 days after the last dose for participants receiving opnurasib as monotherapy or in combination with TNO155 or trametinib, 2. 60 days after the last dose for participants receiving opnurasib in combination with cetuximab, and 3. 150 days after the last dose for participants receiving opnurasib in combination with tislelizumab. |
| Number of participants with dose adjustments | Assessed up to approximately 3 years | The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm. |
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed