A Phase I/II Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors.
Considering participating in a START clinical trial?
Study Summary
To evaluate the safety, tolerability, and preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors.
This study consists of 2 parts:
Phase 1a dose escalation to evaluate LY3537982 monotherapy and
Phase 1b dose expansion to evaluate both LY3537982 monotherapy and in combination.
To determine the RP2D, safety, PK, and antitumor activity per RECIST v1.1.
The study includes a Phase 1a dose escalation phase of olomorasib monotherapy in KRAS G12C-mutant solid tumors and a Phase 1b dose expansion and optimization phase which are evaluating olomorasib as a monotherapy and in combination with other treatments.
To study pembrolizumab plus olomorasib, a potent and highly selective second-generation inhibitor of GDP-bound KRAS G12C, in NSCLC patients treated on LOXO-RAS-20001, a phase 1/2 study of olomorasib in KRAS G12C-mutant solid tumors
Safety was evaluated across all pts dosed with the combination. Antitumor activity per RECIST v1.1 was studied in all pts who had ≥1 post-baseline response assessment (PBRA) or had discontinued before the first PBRA.
Adverse events (AE) were assessed across all treated patients; objective response rate (ORR) per RECIST v1.1 was assessed in patients with at least one post-baseline response assessment or who had discontinued treatment before the first response assessment.
Safety was assessed in all treated pts. IC response by modified RECIST v1.1 in ≥1 measurable (≥5 mm) IC lesion was evaluated in pts with at least one post-baseline response assessment or who discontinued treatment before the first assessment.
- 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
- Any PD-L1 level (0-100%, via local testing) was permitted; and patients needing timely 1L therapy were permitted one cycle of SOC therapy prior to enrollment.
- 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.
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.