LY3537982 + Immunotherapy/Chemotherapy for Non-Small Cell Lung Cancer

(SUNRAY-01 Trial)

Recruiting at 514 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Folic acid, Vitamin B12

Must not be taking: NSAIDs, Aspirin

Disqualifiers: EGFR, ALK, BRAF, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

1016 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, LY3537982, combined with standard treatments for patients with advanced lung cancer that have a specific genetic mutation. The goal is to see if this combination works better than the usual treatments alone.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on aspirin or NSAIDs, you may need to interrupt them. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for non-small cell lung cancer?

Pembrolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer, especially those with high PD-L1 expression, as demonstrated in clinical trials where it significantly increased overall survival compared to chemotherapy. ^{1 2 3 4 5}

Is the combination of LY3537982 and immunotherapy/chemotherapy safe for humans?

Pembrolizumab (Keytruda), an immunotherapy drug, has been used safely in various cancers, including non-small cell lung cancer and melanoma. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can affect the lungs, liver, and thyroid. The benefits of pembrolizumab have been shown to outweigh these risks in life-threatening conditions. ^{1 2 3 6 7}

What makes the drug LY3537982 combined with pembrolizumab unique for treating non-small cell lung cancer?

The combination of LY3537982, a KRAS G12C inhibitor, with pembrolizumab, an immunotherapy drug that blocks the PD-1 pathway, is unique because it targets a specific genetic mutation (KRAS G12C) in cancer cells while also enhancing the immune system's ability to fight cancer, offering a novel approach compared to standard treatments that typically do not target this mutation. ^{1 2 3 8 9}

Research Team

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)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for adults with advanced Non-Small Cell Lung Cancer (NSCLC) that has a specific KRAS G12C gene change. They should have measurable disease, expect to live at least 12 weeks, be able to swallow pills, and not be on breastfeeding. Women who can have children must test negative for pregnancy and agree to use birth control. People with certain other cancer genes or brain metastases, those who can't stop taking NSAIDs, or had prior treatment for NSCLC (except one cycle), cannot join.

Inclusion Criteria

More than or equal to 50%.

I am capable of becoming pregnant and have a negative pregnancy test.

You need to have a disease that can be measured using specific guidelines.

Exclusion Criteria

My cancer has a specific genetic change that can be targeted with treatment.

I've had one round of treatment for advanced lung cancer due to urgent medical need.

My lung cancer is not squamous or mixed small cell/non-small cell type.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Participants receive LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum in 21-day cycles to assess safety

21 days per cycle

Dose Optimization

Participants receive LY3537982 at different dose levels plus Pembrolizumab in 21-day cycles to determine optimal dosing

21 days per cycle

Part A

Participants receive LY3537982 plus Pembrolizumab or Placebo plus Pembrolizumab in 21-day cycles

21 days per cycle

Part B

Participants receive LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum or Placebo plus Pembrolizumab, Pemetrexed, and Platinum in 21-day cycles

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• LY3537982
• Pembrolizumab
• Pemetrexed

Trial Overview The study tests if LY3537982 combined with standard cancer drugs like Pembrolizumab and chemotherapy (Cisplatin or Carboplatin plus Pemetrexed) works better than the standard care alone in treating NSCLC with KRAS G12C mutation. Some participants will also receive a placebo instead of LY3537982.

Participant Groups

Group I: Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum Experimental Treatment 5 Interventions

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.

Group II: Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum Experimental Treatment 5 Interventions

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.

Group III: Part A: LY3537982 plus Pembrolizumab Experimental Treatment 2 Interventions

LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Group IV: Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab Experimental Treatment 2 Interventions

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.

Group V: Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab Experimental Treatment 2 Interventions

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.

Group VI: Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum Placebo Group 5 Interventions

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.

Group VII: Part A: Placebo plus Pembrolizumab Placebo Group 2 Interventions

Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Loxo Oncology, Inc.

Industry Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 807 patients with advanced non-small cell lung cancer (NSCLC) receiving first-line pembrolizumab, the median real-world time on treatment was 7.4 months for those with good performance status (ECOG PS 0-1), indicating a long-term benefit of this therapy.

Patients with KRAS mutations and those with wild-type KRAS had similar treatment durations (7.6 months vs. 7.0 months), suggesting that pembrolizumab is effective regardless of KRAS mutation status in patients with high PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data. Velcheti, V., Hu, X., Li, Y., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Adjuvant platinum-based chemotherapy is the standard treatment for patients with resected non-small-cell lung cancer (NSCLC) stage IB to IIIA, but many still face disease recurrence, highlighting the need for more effective therapies.

The ALCHEMIST trial is investigating the efficacy of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy to potentially improve outcomes compared to standard chemotherapy alone, with the aim of reducing recurrence rates in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). Sands, JM., Mandrekar, SJ., Kozono, D., et al.[2022]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]