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 (SUNRAY-01)

Lilly

Status and phase

Enrolling

Phase 3

Conditions

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Treatments

Drug: Carboplatin

Drug: Pemetrexed

Drug: Cisplatin

Drug: Placebo

Drug: LY3537982

Drug: Pembrolizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT06119581

2023-503412-33-00 (Other Identifier)

U1111-1288-0565 (Other Identifier)

18612

J3M-MC-JZQB (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to assess if adding LY3537982 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.

Full description

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

Enrollment

1,016 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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%.
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
Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
Is unable or unwilling to take folic acid or vitamin B12 supplementation.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

1,016 participants in 7 patient groups, including a placebo group

Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab

Experimental group

Description:

LY3537982 Dose level 1 administered orally in combination with pembrolizumab administered intravenously (IV) in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: LY3537982

Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab

Experimental group

Description:

LY3537982 Dose level 2 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: LY3537982

Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum

Experimental group

Description:

LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: LY3537982

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin

Part A: LY3537982 plus Pembrolizumab

Experimental group

Description:

LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: LY3537982

Part A: Placebo plus Pembrolizumab

Placebo Comparator group

Description:

Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: Placebo

Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum

Experimental group

Description:

Treatment:

Drug: Pembrolizumab

Drug: LY3537982

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin

Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum

Placebo Comparator group

Description:

Placebo administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Treatment:

Drug: Pembrolizumab

Drug: Placebo

Drug: Cisplatin

Drug: Pemetrexed

Drug: Carboplatin