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
PHASE3RECRUITING
The purpose of this study is to assess if adding LY3537982 (olomorasib) in combination with standard of care anti-cancer drugs is more effective than standard of care in participants with untreated advanced NSCLC. NSCLC must have a change in a gene called KRAS G12C. Study participation, including follow-up, could last up to 3 years, depending on how you and your lung cancer are doing.
Study details:
Dose Optimization, Part A, and Part B are randomized. Safety Lead-In for Part B is single arm, non-randomized.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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 pemetrexed label).
- Must have disease with evidence of KRAS G12C mutation.
- Must have known programmed death-ligand 1 (PD-L1) expression
- Part A: Greater than or equal to (≥)50 percent (%).
- Part B: 0% to 100%.
- Must have measurable disease per RECIST v1.1.
- Must have an ECOG performance status of 0 or 1.
- Estimated life expectancy ≥12 weeks.
- Ability to swallow capsules.
- Must have adequate laboratory parameters.
- Contraceptive use should be consistent with local regulations for those participating in clinical studies.
- Women of childbearing potential must
- Have a negative pregnancy test.
- Not be breastfeeding during treatment
Exclusion criteria
- Have a documented additional validated targetable oncogenic driver mutation or alteration in genes such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), BRAF (V600E), human epidermal growth factor receptor 2 (HER2), MET (exon 14), ROS1, rearranged during transfection (RET), or neurotrophic tyrosine receptor kinase (NTRK)1/2/3.
- Have had any of the following prior to randomization:
- Prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for advanced or metastatic NSCLC.
- 1 cycle of standard-of-care treatment prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated:
- Have known active central nervous system metastases and/or carcinomatous meningitis.
- Exclusion Criteria for Participants receiving Pemetrexed and Platinum (Part B and Safety Lead-In Part B)
- Have predominantly squamous cell histology for NSCLC
- Only for participants with mild to moderate renal insufficiency: Unable to avoid aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs) two days before (5 days for long acting NSAIDs), day of, and two days after administration of pemetrexed
- Is unable or unwilling to take folic acid or vitamin B12 supplementation.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT06119581
Intervention or treatment
DRUG: LY3537982
DRUG: Pembrolizumab
DRUG: Placebo
DRUG: Cisplatin
DRUG: Carboplatin
DRUG: Pemetrexed
Conditions
- Carcinoma, Non-Small-Cell Lung
- Neoplasm Metastasis
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Royal Adelaide Hospital
Select from list below to view details:
Royal Adelaide Hospital
Adelaide, Australia
Icon Cancer Centre Wesley
Auchenflower, Australia
Ballarat Health Services
Ballarat Central, Australia
Sunshine Coast University Hospital
Birtinya, Australia
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Who is running the clinical trial?
ELaC
Eli Lilly and Company
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: Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab
| Drug: LY3537982, Drug: Pembrolizumab |
EXPERIMENTAL: Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab
| Drug: LY3537982, Drug: Pembrolizumab |
EXPERIMENTAL: Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum
| Drug: LY3537982, Drug: Pembrolizumab, Drug: Cisplatin, Drug: Carboplatin, Drug: Pemetrexed |
EXPERIMENTAL: Part A: LY3537982 plus Pembrolizumab
| Drug: LY3537982, Drug: Pembrolizumab |
PLACEBO_COMPARATOR: Part A: Placebo plus Pembrolizumab
| Drug: Pembrolizumab, Drug: Placebo |
EXPERIMENTAL: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum
| Drug: LY3537982, Drug: Pembrolizumab, Drug: Cisplatin, Drug: Carboplatin, Drug: Pemetrexed |
PLACEBO_COMPARATOR: Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum
| Drug: Pembrolizumab, Drug: Placebo, Drug: Cisplatin, Drug: Carboplatin, Drug: Pemetrexed |
EXPERIMENTAL: Part C: LY3537982 plus Pembrolizumab
| Drug: LY3537982, Drug: Pembrolizumab |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE) | Dose Optimization and Safety Lead-In Part B: Number of Participants with a TEAE | Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) |
| Part A and Part B: Progression-Free Survival (PFS) | PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR) | Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Part A and Part B: Overall Survival (OS) | Part A and Part B: OS | Randomization to date of death from any cause. (Estimated as up to 3 years) |
| Part A and Part B: PFS | PFS per RECIST v1.1 by investigator | 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) | ORR per RECIST v1.1 by BICR and Investigator | Randomization to disease progression or death. (Estimated as approximately 1 year) |
| Part A and Part B: Duration of Response (DOR) | DOR per RECIST v1.1 by BICR and Investigator | Date of first evidence of CR or PR to date of disease progression or death from any cause. (Estimated as approximately 1 year) |
| Part A and Part B: Disease Control Rate (DCR): Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD) | DCR per RECIST v1.1 by BICR and Investigator | Randomization to disease progression or death from any cause. (Estimated as approximately 1 year) |
| Part A and Part B: Time to Response (TTR) | TTR per RECIST v1.1 by BICR and Investigator | Time from randomization until the date that measurement criteria for CR or PR (whichever is first recorded) are first met (Estimated as approximately 1 year) |
| Part A and Part B: Intracranial Overall Response Rate (ORR) | Intracranial ORR per Modified RECIST (mRECIST) by BICR | Randomization to intracranial disease progression or death. (Estimated as approximately 1 year) |
| Part A and Part B: Intracranial Duration of Response (DoR) | Intracranial DoR per mRECIST by BICR | Date of first evidence of CR or PR to date of intracranial disease progression or death from any cause. (Estimated as approximately 1 year) |
| Part A and Part B: PFS2 | Part A and Part B: PFS2 by Investigator | Randomization to disease progression on next line of treatment or death from any cause (Estimated as approximately 1 year |
| Part A and Part B: Changes in NSCLC-related symptoms as measured by NSCLC-SAQ | NSCLC-related symptoms are assessed by the NSCLC-SAQ total score, which is computed as the sum of the 5 domains (7 questions) and ranges from 0 to 20. The total score will be calculated if all 7 questions are completed. Higher scores indicate more severe symptomatology. | Randomization through end of treatment (Estimated as approximately 1 year)] |
| Part A and Part B: Time to Worsening of NSCLC-related Symptoms as Measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) | NSCLC symptoms will be assessed using the 7-item NSCLC-SAQ. The NSCLC-SAQ measures overall symptom severity of NSCLC, including cough, pain, dyspnea, fatigue, and poor appetite. Response options range from 0) "Not at all" to 4) "Always" or from 0) "Never" to 4) "Always." The total score ranges from 0-20. Higher scores represent worse symptoms. | Randomization through end of treatment (Estimated as approximately 1 year) |
| Part A and Part B: Changes in physical function, as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning subscale and IL19 | Physical function is assessed by EORTC-QLQ-C30 Physical Functioning scale or IL19. The physical function score is calculated by generating the raw score: (Q1+Q2+Q3+Q4+Q5)/5; and then generating the transformed score: (1-((raw score-1)/3)) x 100. The score ranges from 0 to 100. Higher scores indicate better physical function. | Randomization through end of treatment (Estimated as approximately 1 year) |
| Part A and Part B: Time to Deterioration in Physical Function, as Measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning Subscale and IL19 | The EORTC QLQ-C30 is a 30-question patient-reported instrument used to assess multidimensional health-related quality of life (HRQoL) in cancer patients. Physical functioning is measured by the EORTC-QLQ-30 Physical Function Scale (five items). Response options range from 1) "Not at all" to 4) "Very much." The sum score is linearly transformed to the range 0 - 100. Higher scores represent better physical function. | Randomization through end of treatment (Estimated as approximately 1 year) |
| Part A and Part B: Proportion of Time with High Side-Effect Burden, as Measured by Functional Assessment of Cancer Therapy - General Item 5 (FACT-GP5) | FACT-GP5 is a single-item, patient-reported instrument for assessing overall treatment side-effect burden. Response options range from 0) "Not at all" to 4) "Very much." Higher scores represent higher symptom burden. | Randomization through end of treatment (Estimated as approximately 1 year) |
| Part A and Part B: Change from Baseline in Overall Health-related Quality of Life, as Measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale | The EORTC QLQ-C30 is a 30-question patient-reported instrument used to assess multidimensional HRQoL in cancer patients. Overall HRQoL is measured by the EORTC QLQ-30 Global Health Status/Quality of Life Subscale (two items). Response options range from 1) "very poor" to 7) "excellent." Scores are linearly transformed to the range 0 - 100. Higher scores represent better overall HRQoL. | Randomization through end of treatment (Estimated as approximately 1 year) |
Are you running this trial?If you're a clinic or sponsor, you can claim this study.
References
Clinical Trials Gov: A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung CancerOther trials to consider
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