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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eli Lilly & Co.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Jul 2022 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Loxo Oncology, Inc. on behalf of Eli Lilly and Company

External identifiers

EU CT number

2022-502756-31-00

EudraCT number

2021-000595-12

ClinicalTrials.gov

NCT04956640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

"To identify the RP2D, safety and tolerability, optimal dose, and antitumor activity of LY3537982, administered as monotherapy and in combination with other anticancer therapies, in patients with KRAS G12C-mutant advanced solid tumors"

Secondary objectives 2

1. To evaluate the preliminary antitumor activity of LY3537982, administered as monotherapy and in combination with other anticancer therapies, per Investigator assessed RECIST v1.1 (Phase 1a and 1b) and IRC (Phase 2 [Part F]).
2. To assess the PK of LY3537982, administered as monotherapy and in combination with other anticancer therapies.

Conditions and MedDRA coding

KRAS G12C-Mutant Advanced Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Individuals must be able to provide consent consistent with local regulations and be ≥ 18 years of age at the time of signing the informed consent form
2. Individuals must have measurable disease per RECIST v1.1
3. Individuals must have a solid tumor with a KRAS G12C mutation. Individuals with NSCLC who have progressed on a prior KRAS G12C inhibitor are allowed to enroll but must have KRAS G12C mutation confirmed on a blood or tumor sample collected within 3 months of discontinuing the KRAS G12C inhibitor.
4. "Phase 1a Dose escalation: - Advanced solid tumor - Patients who are not candidates for approved treatment measures Phase 1b Dose expansion Part B: - Cohort B9: Individuals must have previously untreated advanced/metastatic NSCLC. One prior 21-day cycle of the KEYNOTE-189 regimen is allowed before enrollement. Patients must initiate study treatment at the dose levels specified for each planned combination agent. - Cohort B8: Individuals must have at least 1 untreated, active brain metastasis Phase 1b Dose expansion Part C and Dose Optimization Part H: - Individuals must have received at least one prior oxaliplatin or irinotecan-containing regimen for advanced/metastatic CRC Phase 1b Dose expansion Part D - Individuals must have an unresetable solid tumor with a KRAS G12C mutation that is not NSCLC, CRC, or pancreatic cancer Phase 1b Dose expansion Part E - Individuals must have been previously treated with a KRAS G12C inhibitor Phase 2 Part F - Individuals must have unresectable pancreatic cancer with a KRAS G12C mutation Phase 1b Dose Optimization Part G - Individuals must have previously untreated advanced/metastatic NSCLC. One prior 21-day cycle of pembrolizumab is allowed before enrollement.
5. Individuals must have an ECOG performance status of 0 or 1
6. Individuals must have adequate organ function, as measured by blood tests
7. Individuals must have stopped all previous cancer treatments and recovered from the major side effects

Exclusion criteria 7

1. Individual must not have an active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process.
2. Individuals cannot have a second active primary malignancy.
3. Individuals cannot have untreated active CNS metastases and/or carcinomatous meningitis. This does not apply to cohort B8.
4. Individuals cannot have received prior KRAS G12C inhibitor therapy. This does not apply to Phase 1a Dose Escalation backfill, cohort E1, or cohort B4.
5. Individuals that have experienced certain immune-related adverse reactions cannot enroll to cohorts B4, B9, or Part G.
6. "Individuals with the following cannot enroll to cohorts B4, B9, or Part G: - An active autoimmune disease - Received a live vaccine within 30 days of study treatment - Received an organ or tissue transplant - Received radiation treatment to lungs - Received prior systemic therapy (except as allowed in Inclusion Criteria #4) "
7. Patients with measured or calculated creatinine clearance <45mL/min at Cycle 1 Day 1 or withing 48 hours of C1D1 are excluded from Cohort B9

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose limiting toxicity (DLT) rate and DLT-equivalent toxicities
2. Rates of TEAEs, SAEs, deaths, and clinical laboratory abnormalities
3. Antitumor activity of LY3537982

Secondary endpoints 1

1. ORR, BOR, DOR, TTR, DCR, PFS, OS, Intracranial ORR and DOR, Plasma concentration of LY3537982 as moontherapy and when administered in combination: PK parameters including, but not limited ot, AUC, Cmax, Tmax, and degree of accumulation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation

Eli Lilly & Co.

Address

1 Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Eli Lilly & Co.

Contact name

Andrei Chertov

Public contact point

Organisation

Eli Lilly & Co.

Contact name

Andrei Chertov

Third parties 10

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications