Recruiting NCT06119581

A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

Phase III Interventional Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: LY3537982, Pembrolizumab, Placebo, Cisplatin.
Who it may be relevant to: Registry conditions: Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Austria, Belgium, Brazil +24
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression

Overview

The purpose of this study is to assess if adding LY3537982 (olomorasib) in combination with standard of care anti-cancer drugs is more effective than standard of care in participants with untreated advanced NSCLC. NSCLC must have a change in a gene called KRAS G12C. Study participation, including follow-up, could last up to 3 years, depending on how you and your lung cancer are doing.

Detailed description

Dose Optimization, Part A, and Part B are randomized. Safety Lead-In for Part B is single arm, non-randomized. Part C is non-randomized.

Interventions

Drug LY3537982
Administered orally.
Drug Pembrolizumab
Administered IV.
Drug Placebo
Administered orally.
Drug Cisplatin
Administered IV.
Drug Carboplatin
Administered IV.
Drug Pemetrexed
Administered IV.

Primary outcome measures

Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE) [Time frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)]
Part A and Part B: Progression-Free Survival (PFS) [Time frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)]

Secondary outcome measures (12)

Part A and Part B: Overall Survival (OS) [Time frame: Randomization to date of death from any cause. (Estimated as up to 3 years)]
Part A and Part B: PFS [Time frame: Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)]
Part A and Part B: Overall Response Rate (ORR): Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) [Time frame: Randomization to disease progression or death. (Estimated as approximately 1 year)]
Part A and Part B: Duration of Response (DOR) [Time frame: Date of first evidence of CR or PR to date of disease progression or death from any cause. (Estimated as approximately 1 year)]
Part A and Part B: Disease Control Rate (DCR): Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD) [Time frame: Randomization to disease progression or death from any cause. (Estimated as approximately 1 year)]
Part A and Part B: Time to Response (TTR) [Time frame: Time from randomization until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 1 year)]
Part A and Part B: Intracranial Overall Response Rate (ORR) [Time frame: Randomization to intracranial disease progression or death. (Estimated as approximately 1 year)]
Part A and Part B: Intracranial Duration of Response (DoR) [Time frame: Date of first evidence of CR or PR to date of intracranial disease progression or death from any cause. (Estimated as approximately 1 year)]
Part A and Part B: PFS2 [Time frame: Randomization to disease progression on next line of treatment or death from any cause (Estimated as approximately 1 year]
Part A and Part B: Changes in NSCLC-related symptoms as measured by NSCLC-SAQ [Time frame: Randomization through end of treatment (Estimated as approximately 1 year)]]
Part A and Part B: Time to Worsening of NSCLC-related Symptoms as Measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) [Time frame: Randomization through end of treatment (Estimated as approximately 1 year)]
Part A and Part B: Changes in physical function, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning subscale and IL19 [Time frame: Randomization through end of treatment (Estimated as approximately 1 year)]

Eligibility criteria

Inclusion criteria

Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
Part B and Safety Lead-In Part B: the histology of the tumor must be predominantly non-squamous (in line with pemetrexed label).
Must have disease with evidence of KRAS G12C mutation.
Must have known programmed death-ligand 1 (PD-L1) expression

Part A: Greater than or equal to (≥)50 percent (%).
Part B: 0% to 100%.
Part C: <50%.
Must have measurable disease per RECIST v1.1.
Must have an ECOG performance status of 0 or 1.
Estimated life expectancy ≥12 weeks.
Ability to swallow capsules.
Must have adequate laboratory parameters.
Contraceptive use should be consistent with local regulations for those participating in clinical studies.
Women of childbearing potential must

Have a negative pregnancy test.
Not be breastfeeding during treatment

Exclusion criteria

Have a documented additional validated targetable oncogenic driver mutation or alteration in genes such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), BRAF (V600E), human epidermal growth factor receptor 2 (HER2), MET (exon 14), ROS1, rearranged during transfection (RET), or neurotrophic tyrosine receptor kinase (NTRK)1/2/3.
Have had any of the following prior to randomization:

\-- Prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for advanced or metastatic NSCLC.

\--- 1 cycle of standard-of-care treatment prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated:

Have known active central nervous system metastases and/or carcinomatous meningitis.

Exclusion Criteria for Participants receiving Pemetrexed and Platinum (Part B and Safety Lead-In Part B)

Have predominantly squamous cell histology for NSCLC
Only for participants with mild to moderate renal insufficiency: Unable to avoid aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs) two days before (5 days for long acting NSAIDs), day of, and two days after administration of pemetrexed
Is unable or unwilling to take folic acid or vitamin B12 supplementation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Double blind
Primary purpose: Treatment