Health Trials

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

ConditionsCarcinoma, Non-Small-Cell LungNeoplasm Metastasis
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorEli Lilly and Company

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • LY3537982

    Drug

    Administered orally.

  • Pembrolizumab

    Drug

    Administered IV.

  • Placebo

    Drug

    Administered orally.

  • Cisplatin

    Drug

    Administered IV.

  • Carboplatin

    Drug

    Administered IV.

  • Pemetrexed

    Drug

    Administered IV.

Treatment groups

1,264 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Dose Optimization: LY3537982 Dose Level 1 plus PembrolizumabExperimental treatment 2 interventions
Group B: Dose Optimization: LY3537982 Dose Level 2 plus PembrolizumabExperimental treatment 2 interventions
Group C: Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and PlatinumExperimental treatment 5 interventions
Group D: Part A: LY3537982 plus PembrolizumabExperimental treatment 2 interventions
Group E: Part A: Placebo plus PembrolizumabPlacebo comparator 2 interventions
Group F: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and PlatinumExperimental treatment 5 interventions
Group G: Part B: Placebo plus Pembrolizumab, Pemetrexed, and PlatinumPlacebo comparator 5 interventions
Group H: Part C: LY3537982 plus PembrolizumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE)

Dose Optimization and Safety Lead-In Part B: Number of Participants with a TEAE

Time frame
Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)
2

Part A and Part B: Progression-Free Survival (PFS)

PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)

Time frame
Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)

Secondary outcomes

1

Part A and Part B: Overall Survival (OS)

Part A and Part B: OS

Time frame
Randomization to date of death from any cause. (Estimated as up to 3 years)
2

Part A and Part B: PFS

PFS per RECIST v1.1 by investigator

Time frame
Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year)
3

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)

ORR per RECIST v1.1 by BICR and Investigator

Time frame
Randomization to disease progression or death. (Estimated as approximately 1 year)
4

Part A and Part B: Duration of Response (DOR)

DOR per RECIST v1.1 by BICR and Investigator

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)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Eli Lilly and Company

Lead sponsor

Source ClinicalTrials.gov
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