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Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)

PHASE1PHASE2RECRUITING

The purpose of this study is to find out whether the study drug, LY3537982, is safe and effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must have already received or were not able to tolerate the standard of care, except for specific groups who have not had cancer treatment. The study will last up to approximately 4 years.

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Study details:

This is an open-label, multicenter Phase 1/2 study to evaluate safety, tolerability, and preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors. This study will be conducted in 4 parts: Phase 1a dose escalation, Phase 1b dose expansion, Phase 1b dose optimization, and Phase 2. KRAS G12C mutations will be identified through standard of care testing.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Patients have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA).

Participants must have a histological or a cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.

Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Have adequate organ function.

Have discontinued all previous treatments for cancer with resolution of any significant ongoing adverse events (AEs), (except in certain scenarios).

Must be able to swallow capsule/tablet.

Agree and adhere to contraceptive use, if applicable.

For some parts of the study, (i.e., one of the two arms with LY3537982 in combination with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic setting and not suitable for curative intent radical surgery or radiation therapy. Previously untreated patients who received adjuvant and neoadjuvant therapy are eligible if the last dose of the systemic treatment was completed at least 6 months prior to enrollment. For untreated patients in the arm with LY3537982 in combination with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of any or all of the drugs other than LY3537982 may be initiated within 21 days prior to enrollment. Start of study treatment may be delayed to allow sufficient time for recovery from treatment-related toxicity.

For one part of the study, participants must have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.

Exclusion criteria

Disease suitable for local therapy administered with curative intent.

Have an active, ongoing, or untreated infection.

Have a serious pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.

Have a serious cardiac condition.

Have a second active primary malignancy or have been diagnosed and/or treated for an additional malignancy within 3 years prior to enrollment.

For some parts of the study only: have untreated active central nervous system (CNS) metastases and/or leptomeningeal disease. Patients with treated CNS metastases are eligible for this study if their disease is asymptomatic, radiographically stable for at least 30 days, and they do not require treatment with steroids in the two-week period prior to study treatment. Patients with active CNS metastases are eligible for one part of the study.

Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.

The following patients will be excluded from some parts of the study: Experienced certain serious side effects with prior immunotherapy.

Have an active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.

Have received a live vaccine within 30 days prior to the first dose of study drug.

Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 180 days after the last dose of study medication.

Known allergic reaction against any of the components of the study treatments.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2021-07-19

Primary completion: 2026-06-01

Study completion finish: 2026-06-01

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT04956640

Intervention or treatment

DRUG: LY3537982

DRUG: Pembrolizumab

DRUG: Cetuximab

DRUG: Pemetrexed

DRUG: Cisplatin

DRUG: Carboplatin

Conditions

• Carcinoma, Non-Small-Cell Lung
• Colorectal Neoplasms
• Endometrial Neoplasms
• Ovarian Neoplasms
• Pancreatic Neoplasms
• Biliary Tract Neoplasms

Image related to Carcinoma, Non-Small-Cell Lung

Condition: Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms and more
DRUG: LY3537982 and other drugs
St Leonards, New South Wales, Australia and more
Sponsor: Eli Lilly and Company

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Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Royal North Shore Hospital

Research sites nearby

Select from list below to view details:

Royal North Shore Hospital
St Leonards, New South Wales, Australia
Cancer Research SA
Adelaide, South Australia, Australia
Linear Clinical Research
Nedlands, Western Australia, Australia
St Vincent's Hospital Sydney
Sydney, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LY3537982 (Dose Escalation) LY3537982 administered orally.	DRUG: LY3537982 Oral
EXPERIMENTAL: LY3537982 (Dose Expansion) LY3537982 administered orally either alone or with another investigational agent.	DRUG: LY3537982 Oral
EXPERIMENTAL: LY3537982 (Dose Optimization) LY3537982 administered orally either alone or with another investigational agent	DRUG: LY3537982 Oral

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy	Measured by the number of patients with dose-limiting toxicities (DLTs)	Cycle 1 (21 Days)
Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents	Measured by the number of patients with dose-limiting toxicities (DLTs)	Cycle 1 (21 Days)
Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab	Measured by TEAEs	Estimated up to 2 years
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	Not Specified	Estimated up to 2 years
To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation	Not Specified	Estimated up to 2 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)	ORR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)	DOR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)	BOR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)	TTR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)	DCR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)	PFS	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)	OS	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial DOR based on modified RECIST v1.1 (Certain arms of the study only)	Intracranial DOR	Estimated up to 2 years
To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Whole-body ORR based on RECIST v1.1 and modified RECIST v1.1 (Certain arms of the study only)	Whole-body ORR	Estimated up to 2 years
To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)	PK: AUC of LY3537982	Predose estimated up to 2 years
To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)	PK: Cmax of LY3537982	Predose estimated up to 2 years

Frequently Asked Questions

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References

Clinical Trials Gov: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)