A Study of LY3537982 Plus Immunotherapy With or Without Chemotherapy in Participants With Non-Small Cell Lung Cancer (NSCLC) With a Change in a Gene Called KRAS G12C

JRCT ID: jRCT2061230080

Registered date:15/12/2023

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis

• Date of first enrollment: 07/02/2024
• Target sample size: 1016
• Countries of recruitment: Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,India,Japan,Italy,Japan,Korea, Republic of,Japan,Mexico,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

Study Arms
Experimental: Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab
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.
Interventions:
Drug: LY3537982
Drug: Pembrolizumab
Experimental: Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab
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.
Interventions:
Drug: LY3537982
Drug: Pembrolizumab
Experimental: Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum
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.
Interventions:
Drug: LY3537982
Drug: Pembrolizumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Experimental: Part A: LY3537982 plus Pembrolizumab
LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions:
Drug: LY3537982
Drug: Pembrolizumab
Placebo Comparator: Part A: Placebo plus Pembrolizumab
Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions:
Drug: Pembrolizumab
Drug: Placebo
Experimental: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum
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.
Interventions:
Drug: LY3537982
Drug: Pembrolizumab
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Placebo Comparator: Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum
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.
Interventions:
Drug: Pembrolizumab
Drug: Placebo
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed

Outcome(s)

Primary Outcome

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) ]
Dose Optimization and Safety Lead-In Part B: Number of Participants with a TEAE
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) ]
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 and after study intervention for at least 180 days.

Exclude 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)
Squamous cell and/or mixed small cell/nonsmall cell histology is not permitted.
Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
Is unable or unwilling to take folic acid or vitamin B12 supplementation.

Related Information

• Primary Sponsor: Takeshi Masaki
• Secondary ID(s): NCT06119581