Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer, KRAS G12 Lung Cancer, Advanced Lung Cancer, Metastatic Lung Cancer, KRAS G12C inhibitor, KRAS G12C Positive, KRAS Mutation, KRAS G12 Mutation, Lung Cancer Mutation, Olomorasib, Lung Diseases, Neoplastic Processes, Pathologic Processes, Neoplasm Metastasis, Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer (NSCLC), Antineoplastic Agents, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Lung Neoplasms
Brief summary
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.
Detailed description
Dose Optimization, Part A, and Part B are randomized. Safety Lead-In for Part B is single arm, non-randomized. Part C is non-randomized.
Interventions
DRUGLY3537982
Administered orally.
DRUGPembrolizumab
Administered IV.
DRUGPlacebo
Administered orally.
DRUGCisplatin
Administered IV.
DRUGCarboplatin
Administered IV.
DRUGPemetrexed
Administered IV.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Parts A and B are double blind. Dose Optimization, Safety Lead-In for Part B and Part C are open label.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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%. * Part C: \<50%. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE) | Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) | Dose Optimization and Safety Lead-In Part B: Number of Participants with a TEAE |
| Part A and Part B: Progression-Free Survival (PFS) | Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) | PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and Part B: Duration of Response (DOR) | Date of first evidence of CR or PR to date of disease progression or death from any cause. (Estimated as approximately 1 year) | DOR per RECIST v1.1 by BICR and Investigator |
| Part A and Part B: Disease Control Rate (DCR): Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD) | Randomization to disease progression or death from any cause. (Estimated as approximately 1 year) | DCR per RECIST v1.1 by BICR and Investigator |
| Part A and Part B: Time to Response (TTR) | 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) | TTR per RECIST v1.1 by BICR and Investigator |
| Part A and Part B: Intracranial Overall Response Rate (ORR) | Randomization to intracranial disease progression or death. (Estimated as approximately 1 year) | Intracranial ORR per Modified RECIST (mRECIST) by BICR |
| Part A and Part B: Intracranial Duration of Response (DoR) | Date of first evidence of CR or PR to date of intracranial disease progression or death from any cause. (Estimated as approximately 1 year) | Intracranial DoR per mRECIST by BICR |
| Part A and Part B: PFS2 | Randomization to disease progression on next line of treatment or death from any cause (Estimated as approximately 1 year | Part A and Part B: PFS2 by Investigator |
| Part A and Part B: Changes in NSCLC-related symptoms as measured by NSCLC-SAQ | Randomization through end of treatment (Estimated as approximately 1 year)] | 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. |
| Part A and Part B: Time to Worsening of NSCLC-related Symptoms as Measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) | Randomization through end of treatment (Estimated as approximately 1 year) | 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. |
| 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 | Randomization through end of treatment (Estimated as approximately 1 year) | 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. |
| Part A and Part B: Overall Survival (OS) | Randomization to date of death from any cause. (Estimated as up to 3 years) | Part A and Part B: OS |
| 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 | Randomization through end of treatment (Estimated as approximately 1 year) | 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. |
| 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) | Randomization through end of treatment (Estimated as approximately 1 year) | 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. |
| Part A and Part B: PFS | Randomization to first documented progression of disease or death from any cause. (Estimated as approximately 1 year) | PFS per RECIST v1.1 by investigator |
| 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 | Randomization through end of treatment (Estimated as approximately 1 year) | 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. |
| 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) | Randomization to disease progression or death. (Estimated as approximately 1 year) | ORR per RECIST v1.1 by BICR and Investigator |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed