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LY3537982

Phase 3

Carcinoma, Non-Small-Cell Lung | Small molecule | Oncology |Eli Lilly and Company|Last Updated: Aug 24, 2026

Target and mechanism

Molecular targetKRAS G12C
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment1,804

FDA Designations

No designations recorded

Clinical trial landscape

LY3537982 · 8 trials · 10 indications

Phase 3 1Phase 1 7
NCT06119581A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung CancerCarcinoma, Non-Small-Cell Lung
RECRUITING1,264 Analytics
PHASE3RECRUITING
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
Carcinoma, Non-Small-Cell LungUnlock trial analytics

Study Endpoints

Primary Endpoints

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

Pharmacokinetics: Maximum Concentration (Cmax) of LY3537982
Day 1, Predose up to Day 5 Postdose
Pharmacokinetics: Area Under the Concentration Verses Time Curve from Time Zero to Infinity (AUC[0-∞]) of LY3537982
Day 1, Predose up to Day 5 Postdose
Pharmacokinetics: Area Under the Concentrations Verses Time Curve from Time Zero to Time t (AUC(0-tlast) of LY3537982
Day 1, Predose up to Day 5 Postdose
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of LY3537982
Predose approximately up to 18 weeks

PK: Cmax of LY3537982

PK: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3537982
Predose approximately up to 18 weeks

PK: AUC of LY3537982

Part 1: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3537982
Predose on day 11 up to day 17

Part 1: PK: Cmax of LY3537982

Part 1: PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUC[0-inf]) of LY3537982
Predose on day 11 up to day 17

Part 1: PK: AUC\[0-inf\] of LY3537982

Part 1: PK: AUC from Time 0 to time of the last measurable concentration (AUClast) of LY3537982
Predose on day 11 up to day 17

Part 1: PK: AUClast of LY3537982

Part 1: PK: Cmax of Digoxin
Predose on day 1 up to day 21
Part 1: PK: AUC[0-inf] of Digoxin
Predose on day 1 up to day 21

Part 1: PK: AUC\[0-inf\] of Digoxin

Part 1: PK: AUClast of Digoxin
Predose on day 1 up to day 21
Part 1: PK: Cmax of Rosuvastatin
Predose on day 1 up to day 21
Part 1: PK: AUC[0-inf] of Rosuvastatin
Predose on day 1 up to day 21

Part 1: PK: AUC\[0-inf\] of Rosuvastatin

Part 1: PK: AUClast of Rosuvastatin
Predose on day 1 up to day 21
Part 2: PK: Cmax of LY3537982
Predose on day 4 up to day 11
Part 2: PK: AUC[0-inf] of LY3537982
Predose on day 4 up to day 11

Part 2: PK: AUC\[0-inf\] of LY3537982

Part 2: PK: AUClast of LY3537982
Predose on day 4 up to day 11
Part 2: PK: Cmax of Midazolam
Predose on day 1 up to day 9
Part 2: PK: AUC[0-inf] of Midazolam
Predose on day 1 up to day 9

Part 2: PK: AUC\[0-inf\] of Midazolam

Part 2: PK: AUClast of Midazolam
Predose on day 1 up to day 9
Part 2: PK: Cmax of 1'-Hydroxymidazolam
Predose on day 1 up to day 9
Part 2: PK: AUC[0-inf] of 1'-Hydroxymidazolam
Predose on day 1 up to day 9

Part 2: PK: AUC\[0-inf\] of 1'-Hydroxymidazolam

Part 2: PK: AUClast of 1'-Hydroxymidazolam
Predose on day 1 up to day 9
Pharmacokinetics (PK): Fraction of Dose Excreted in Urine (Feur)
Predose on day 1 up to postdose on day 21 (Part 1)

PK: Feur

PK: Cumulative Feur
Predose on day 1 up to postdose on day 21 (Part 1)
PK: Fraction of Dose Excreted in Feces (Fefeces)
Predose on day 1 up to postdose on day 21 (Part 1)

PK: Fefeces

PK: Cumulative Fefeces
Predose on day 1 up to postdose on day 21 (Part 1)
PK: Fraction of Dose Excreted in Expired Air (Feair)
Predose on day 1 up to postdose on day 21 (Part 1)

PK: Feair

PK: Absolute Bioavailability (F) of LY3537982
Predose on day 1 up to postdose on day 9 (Part 2)

PK: F of LY3537982

Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3537982 administered with or without itraconazole
Predose on day 1 up to 72 hours postdose on day 9

PK: Cmax of LY3537982 administered with or without itraconazole

PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUC[0-inf]) of LY3537982 administered with or without itraconazole
Predose on day 1 up to 72 hours postdose on day 9

PK: AUC\[0-inf\] of LY3537982 administered with or without itraconazole

PK: AUC from Time 0 to time of the last measurable concentration (AUClast) of LY3537982 administered with or without itraconazole
Predose on day 1 up to 72 hours postdose on day 9

PK: AUClast of LY3537982 administered with or without itraconazole

PK: Cmax of LY3537982 administered with or without carbamazepine
Predose on day 1 up to 72 hours postdose on day 13
PK: AUC[0-inf] of LY3537982 administered with or without carbamazepine
Predose on day 1 up to 72 hours postdose on day 13

PK: AUC\[0-inf\] of LY3537982 administered with or without carbamazepine

PK: AUClast of LY3537982 administered with or without carbamazepine
Predose on day 1 up to 72 hours postdose on day 13
Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUC[0-inf])
Day 1 and Day 4 of each study period

PK: AUC(0-inf)

PK: Maximum Observed Concentration (Cmax) of LY3537982
Day 1 and Day 4 of each study period

PK: Cmax of LY3537982

Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy
Cycle 1 (21 Days)

Measured by the number of patients with dose-limiting toxicities (DLTs)

Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents
Cycle 1 (21 Days)

Measured by the number of patients with dose-limiting toxicities (DLTs)

Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab
Estimated up to 2 years

Measured by TEAEs

To determine the optimal dose of LY3537982 to be administered to participants who have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC in combination with cetuximab
Estimated up to 2 years
To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation
Estimated up to 2 years

Secondary Endpoints

Part A and Part B: Overall Survival (OS)
Randomization to date of death from any cause. (Estimated as up to 3 years)
Part A and Part B: PFS
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)
Randomization to disease progression or death. (Estimated as approximately 1 year)
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Dose Optimization: LY3537982 Dose Level 1 plus PembrolizumabEXPERIMENTALLY3537982 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.
Dose Optimization: LY3537982 Dose Level 2 plus PembrolizumabEXPERIMENTALLY3537982 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.
Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and PlatinumEXPERIMENTALLY3537982 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.
Part A: LY3537982 plus PembrolizumabEXPERIMENTALLY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Placebo plus PembrolizumabPLACEBO_COMPARATORPlacebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and PlatinumEXPERIMENTALLY3537982 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.
Part B: Placebo plus Pembrolizumab, Pemetrexed, and PlatinumPLACEBO_COMPARATORPlacebo 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.
Part C: LY3537982 plus PembrolizumabEXPERIMENTALLY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
LY3537982 (Normal renal function)EXPERIMENTALLY3537982 administered orally.
LY3537982 (Severe renal impairment)EXPERIMENTALLY3537982 administered orally.
LY3537982 (Moderate renal impairment)EXPERIMENTALLY3537982 administered orally.
LY3537982EXPERIMENTALLY3537982 administered orally.
LY3537982 + Digoxin & Rosuvastatin (Part 1)EXPERIMENTALSingle oral doses of digoxin and rosuvastatin with or without multiple doses of LY3537982 administered orally
LY3537982 + Midazolam (Part 2)EXPERIMENTALSingle doses of midazolam administered either orally or intravenously (IV) with or without multiple doses of LY3537982 administered orally
[¹⁴C]-LY3537982 (Part 1)EXPERIMENTALSingle dose of \[¹⁴C\]-LY3537982 administered orally.
[¹⁴C]-LY3537982 + LY3537982 (Part 2)EXPERIMENTALSingle dose of LY3537982 administered orally followed by \[¹⁴C\]-LY3537982 administered intravenously (IV).
LY3537982 + Itraconazole (Part 1)EXPERIMENTALLY3537982 administered orally alone followed by LY3537982 administered in combination with itraconazole orally.
LY3537982 + Carbamazepine (Part 2)EXPERIMENTALLY3537982 administered orally alone followed by LY3537982 administered in combination with carbamazepine orally.
LY3537982 (High-Fat Meal)EXPERIMENTALLY3537982 administered orally under fasting conditions in one study period and under fed conditions (i.e., a standard high-fat meal) in the other study period.
LY3537982 (Low-Fat Meal)EXPERIMENTALLY3537982 administered orally under fasting conditions in one study period and under fed conditions (i.e., a standard low-fat meal) in the other study period.
LY3537982 (Dose Escalation)EXPERIMENTALLY3537982 administered orally.
LY3537982 (Dose Expansion)EXPERIMENTALLY3537982 administered orally either alone or with another investigational agent.
LY3537982 (Dose Optimization)EXPERIMENTALLY3537982 administered orally either alone or with another investigational agent

Interventions

NameTypeDescription
LY3537982DRUGAdministered orally.
PembrolizumabDRUGAdministered IV.
PlaceboDRUGAdministered orally.
CisplatinDRUGAdministered IV.
CarboplatinDRUGAdministered IV.
PemetrexedDRUGAdministered IV.
DigoxinDRUGAdministered orally
RosuvastatinDRUGAdministered orally
MidazolamDRUGAdministered orally
[¹⁴C]-LY3537982DRUGAdministered orally.
ItraconazoleDRUGAdministered orally.
CarbamazepineDRUGAdministered orally.
CetuximabDRUGIntravenous
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites418

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 peme...

Countries:United StatesAustraliaAustriaBelgiumBrazilCanadaChinaCzechiaDenmarkFranceGermanyGreeceHungaryIndiaItalyJapanMexicoNetherlandsNorwayPolandPortugalRomaniaSouth KoreaSpainSwedenSwitzerlandTaiwanTurkey (Türkiye)United Kingdom
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Recent Changes (Last 90 Days)

LOWAug 24, 2026NCT06119581lastUpdatePostDate: changed
LOWAug 24, 2026NCT06119581lastUpdatePostDate: changed
LOWJul 20, 2026NCT06119581lastUpdatePostDate: changed
LOWJul 20, 2026NCT06119581lastUpdatePostDate: changed
LOWJul 7, 2026NCT06119581lastUpdatePostDate: changed
LOWJul 7, 2026NCT06119581lastUpdatePostDate: changed
MEDIUMJun 29, 2026NCT06235983TRIAL_REMOVED: changed
MEDIUMJun 29, 2026NCT06235983TRIAL_REMOVED: changed
MEDIUMJun 29, 2026NCT06235983TRIAL_REMOVED: changed
LOWJun 18, 2026NCT06119581lastUpdatePostDate: changed
LOWJun 18, 2026NCT06119581lastUpdatePostDate: changed
LOWJun 18, 2026NCT06119581lastUpdatePostDate: changed

Frequently asked questions about LY3537982

What is LY3537982 used for?

LY3537982 is an investigational small molecule being studied for advanced solid tumors, carcinoma, non-small-cell lung cancer, and renal insufficiency. It is being evaluated in patients with KRAS G12C mutations, including those with non-small-cell lung cancer, colorectal, endometrial, ovarian, pancreatic, and biliary tract neoplasms.

What does LY3537982 target?

LY3537982 targets KRAS G12C, a specific genetic mutation found in certain cancers. By targeting this mutant form of the KRAS protein, the drug is designed to interfere with cancer cell growth driven by this mutation.

Who makes LY3537982?

LY3537982 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the NYSE under the ticker LLY.

What phase is LY3537982 in?

LY3537982 is in clinical development. It has been studied in Phase 1 trials for advanced solid tumors and renal insufficiency, and is currently being evaluated in a Phase 3 trial for first-line advanced KRAS G12C-mutant non-small cell lung cancer.

What clinical trials is LY3537982 in?

LY3537982 is being studied in several trials. NCT04956640 is a Phase 1 study in cancer patients with KRAS G12C mutations. NCT06119581 is a Phase 3 trial combining LY3537982 with pembrolizumab and chemotherapy in non-small cell lung cancer. NCT06235983 and NCT07137689 are completed Phase 1 studies in Chinese participants and those with kidney problems.

Is LY3537982 the same as olomorasib?

Yes, LY3537982 is also known as olomorasib. In clinical trial NCT06119581, the drug is referred to as olomorasib (LY3537982), confirming that both names refer to the same investigational agent.