Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
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| ClinicalTrials.gov Identifier: NCT04956640 |
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Recruitment Status :
Recruiting
First Posted : July 9, 2021
Last Update Posted : April 18, 2024
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Sponsor:
Eli Lilly and Company
Collaborators:
Loxo Oncology, Inc.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Eli Lilly and Company
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Endometrial Neoplasms Ovarian Neoplasms Pancreatic Neoplasms Biliary Tract Neoplasms | Drug: LY3537982 Drug: Pembrolizumab Drug: Cetuximab Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin | Phase 1 Phase 2 |
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 3 parts: Phase 1a dose escalation, Phase 1b dose expansion and dose optimization, and Phase 2.
KRAS G12C mutations will be identified through standard of care testing.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 450 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors |
| Actual Study Start Date : | July 19, 2021 |
| Estimated Primary Completion Date : | September 2025 |
| Estimated Study Completion Date : | September 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: LY3537982 (Dose Escalation)
LY3537982 administered orally.
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Drug: LY3537982
Oral |
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Experimental: LY3537982 (Dose Expansion)
LY3537982 administered orally either alone or with another investigational agent.
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Drug: LY3537982
Oral Drug: Pembrolizumab Intravenous
Other Name: Keytruda Drug: Cetuximab Intravenous
Other Name: Erbitux Drug: Pemetrexed Intravenous
Other Names:
Drug: Cisplatin Intravenous Drug: Carboplatin Intravenous |
Primary Outcome Measures :
- Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Estimated up to 2 years ]
- To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation [ Time Frame: Estimated up to 2 years ]
Secondary Outcome Measures :
- To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR) [ Time Frame: Estimated up to 2 years ]ORR
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR) [ Time Frame: Estimated up to 2 years ]DOR
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR) [ Time Frame: Estimated up to 2 years ]BOR
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR) [ Time Frame: Estimated up to 2 years ]TTR
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR) [ Time Frame: Estimated up to 2 years ]DCR
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS) [ Time Frame: Estimated up to 2 years ]PFS
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS) [ Time Frame: Estimated up to 2 years ]OS
- To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial ORR based on modified RECIST v1.1 (Certain arms of the study only) [ Time Frame: Estimated up to 2 years ]Intracranial ORR
- 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) [ Time Frame: Estimated up to 2 years ]Intracranial DOR
- 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) [ Time Frame: Estimated up to 2 years ]Whole-body ORR
- To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC) [ Time Frame: Predose estimated up to 2 years ]PK: AUC of LY3537982
- To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax) [ Time Frame: Predose estimated up to 2 years ]PK: Cmax of LY3537982
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
- Have symptomatic central nervous system (CNS) malignancy or metastasis and/or carcinomatous meningitis. 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. This only applies to some parts 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.
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04956640
Contacts
| Contact: Patient Advocacy | 855-569-6305 | clinicaltrials@loxooncology.com |
Locations
Show 32 study locations
Sponsors and Collaborators
Eli Lilly and Company
Loxo Oncology, Inc.
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Melinda Willard, PhD | Loxo Oncology, Inc. |
Additional Information:
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT04956640 |
| Other Study ID Numbers: |
LOXO-RAS-20001 2021-000595-12 ( EudraCT Number ) J3M-OX-JZQA ( Other Identifier: Eli Lilly and Company ) KEYNOTE E27 ( Other Identifier: Merck ) |
| First Posted: | July 9, 2021 Key Record Dates |
| Last Update Posted: | April 18, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Eli Lilly and Company:
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Frontline 1L First Line |
Additional relevant MeSH terms:
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Neoplasms Colorectal Neoplasms Carcinoma, Non-Small-Cell Lung Pancreatic Neoplasms Ovarian Neoplasms Endometrial Neoplasms Biliary Tract Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases |
Rectal Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Endocrine Gland Neoplasms Pancreatic Diseases Endocrine System Diseases Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases |