A Study of LY3537982 Plus Immunotherapy With or Without Chemotherapy in Participants With Non-Small Cell Lung Cancer (NSCLC) With a Change in a Gene Called KRAS G12C (SUNRAY-01)

• ClinicalTrials.gov Identifier: NCT06119581
• Recruitment Status: Recruiting
• First Posted: November 7, 2023
• Last Update Posted: May 6, 2024
• Sponsor: Eli Lilly and Company
• Collaborator: Loxo Oncology, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: November 1, 2023
• First Posted Date: November 7, 2023
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: December 21, 2023
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2023)

• Dose Optimization and Safety Lead-In Part B: Number of Participants with a Treatment Emergent Adverse Event(s) (TEAE) [ Time Frame: 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) [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 1, 2023)

• Part A and Part B: Overall Survival (OS) [ Time Frame: 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: Overall Response Rate (ORR): Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) [ Time Frame: Randomization to disease progression or death. (Estimated as approximately 1 year) ]
  ORR per RECIST v1.1 by BICR
• Part A and Part B: Duration of Response (DOR) [ Time Frame: 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
• Part A and Part B: Disease Control Rate (DCR): Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD) [ Time Frame: Randomization to disease progression or death from any cause. (Estimated as approximately 1 year) ]
  DCR per RECIST v1.1 by BICR
• Part A and Part B: Time to Response (TTR) [ Time Frame: 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
• Part A and Part B: PFS2 [ Time Frame: 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: Time to Worsening of NSCLC-related Symptoms as Measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) [ Time Frame: 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: 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 [ Time Frame: 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) [ Time Frame: 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: Change from Baseline in Overall Health-related Quality of Life, as Measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LY3537982 Plus Immunotherapy With or Without Chemotherapy in Participants With Non-Small Cell Lung Cancer (NSCLC) With a Change in a Gene Called KRAS G12C
• Official Title: SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression
• Brief Summary: The purpose of this study is to assess if adding LY3537982 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Carcinoma, Non-Small-Cell Lung
• Neoplasm Metastasis

Intervention

• Drug: LY3537982
  Administered orally.
• Drug: Pembrolizumab
  Administered IV.
• Drug: Placebo
  Administered orally.
• Drug: Cisplatin
  Administered IV.
• Drug: Carboplatin
  Administered IV.
• Drug: Pemetrexed
  Administered IV.

Study Arms

• Experimental: Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab
  LY3537982 Dose level 1 administered orally in combination with pembrolizumab administered intravenously (IV) in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: LY3537982
  • Drug: Pembrolizumab
• Experimental: Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab
  LY3537982 Dose level 2 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: LY3537982
  • Drug: Pembrolizumab
• Experimental: Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum
  LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: LY3537982
  • Drug: Pembrolizumab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Pemetrexed
• Experimental: Part A: LY3537982 plus Pembrolizumab
  LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: LY3537982
  • Drug: Pembrolizumab
• Placebo Comparator: Part A: Placebo plus Pembrolizumab
  Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Placebo
• Experimental: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum
  LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: LY3537982
  • Drug: Pembrolizumab
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Pemetrexed
• Placebo Comparator: Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum
  Placebo administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Placebo
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: Pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 1, 2023): 1016
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2029
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 and after study intervention for at least 180 days.

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)

• Squamous cell and/or mixed small cell/nonsmall cell histology is not permitted.
• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Is unable or unwilling to take folic acid or vitamin B12 supplementation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT06119581
• Other Study ID Numbers: 18612; J3M-MC-JZQB ( Other Identifier: Eli Lilly and Company ); U1111-1288-0565 ( Other Identifier: Universal Trial Number ); 2023-503412-33-00 ( Other Identifier: EU Trial Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Loxo Oncology, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2024