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

(SUNRAY-01 Trial)

Recruiting at 596 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a new drug, LY3537982 (a KRAS G12C inhibitor), to standard cancer treatments benefits people with advanced non-small cell lung cancer (NSCLC) with a specific gene change called KRAS G12C. The research compares different combinations of LY3537982 with other cancer drugs, including pembrolizumab, to determine the most effective treatment. Individuals who have not received advanced lung cancer treatment and have the KRAS G12C mutation may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LY3537982, when combined with pembrolizumab, is generally safe, with most people tolerating it without serious side effects. In some studies, this combination has also shown promise in fighting tumors, indicating potential effectiveness.

When combined with pembrolizumab, pemetrexed, and platinum-based drugs like cisplatin or carboplatin, LY3537982 still appears safe, without causing unexpected or dangerous side effects.

Overall, the safety data for LY3537982, when used with other cancer treatments, is encouraging, with many participants managing the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LY3537982 because it represents a fresh approach for treating non-small cell lung cancer (NSCLC). Unlike standard treatments, which often rely solely on chemotherapy or existing immunotherapies like pembrolizumab, LY3537982 is combined with pembrolizumab, pemetrexed, and a platinum-based drug, offering a potentially more effective multi-faceted attack on cancer cells. This new combination aims to enhance the immune response and improve the overall effectiveness of treatment, potentially offering better outcomes for patients who might not respond as well to current options.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that LY3537982, also known as olomorasib, could be a promising treatment for non-small cell lung cancer (NSCLC) with a specific gene change called KRAS G12C. Early studies have found that LY3537982 is safe and may work well in patients with this gene change. In this trial, some participants will receive LY3537982 with pembrolizumab, an immunotherapy drug, and it has been safe and well-tolerated in these patients. Other participants will receive LY3537982 combined with pembrolizumab, pemetrexed, and platinum-based chemotherapy (cisplatin or carboplatin), which might enhance the treatment's effectiveness, as similar combinations have shown promise in other treatments. Overall, the evidence is encouraging for using LY3537982 with other cancer treatments to address advanced NSCLC. ^{6 7 8 9 10}

Who Is on the Research Team?

Call 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)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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 are expected to live for at least 12 more weeks.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39127176/

Efficacy and Safety of KRASG12C Inhibitor IBI351 ... Conclusions: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new ...

2. onclive.com onclive.com/view/ly3537982-demonstrates-tolerability-and-preliminary-efficacy-in-kras-g12c-mutated-advanced-solid-tumors

LY3537982 Demonstrates Tolerability and Preliminary ... The favorable safety and preliminary efficacy demonstrated by the LY3537982 at multiple dose levels in patients with KRAS G12C–mutated advanced solid tumors

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11352592/

KRASG12C Inhibitors in Non-Small Cell Lung Cancer: A Review In this review, from the aspect of brain metastasis, we aim to provide an overview of the advances in therapies that target KRAS G12C.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00040

Single-Agent Divarasib in Patients With <i>KRAS G12C</i> Overall, 65 patients with advanced KRAS G12C–positive NSCLC received single-agent oral divarasib 50-400 mg once daily and 31 patients (48%) were ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925000826

Real-world effectiveness and tolerability of sotorasib in ... This study gave insights into effectiveness and safety of sotorasib in a real-world setting, in advanced or metastatic KRAS G12C-mutated non-squamous NSCLC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06119581

NCT06119581 | A Study of First-Line Olomorasib ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907553/

Immunotherapy in advanced, KRAS G12C-mutant non- ... This review explores the emerging therapeutic strategies in KRAS G12C-mutant NSCLC, including dual checkpoint blockade and combinations with checkpoint ...

8. merck.com merck.com/news/merck-initiates-phase-3-clinical-trial-of-mk-1084-an-investigational-oral-kras-g12c-inhibitor-in-combination-with-keytruda-pembrolizumab-for-first-line-treatment-of-certain-patients-with-met/

Merck Initiates Phase 3 Clinical Trial of MK-1084, an ... “Based on early evidence showing MK-1084 in combination with KEYTRUDA had a manageable safety profile and promising anti-tumor activity, we are ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8519

Safety and efficacy of olomorasib + immunotherapy in first- ... Olomorasib + pembrolizumab in the 1L metastatic setting demonstrated favorable safety and encouraging antitumor activity in pts with KRAS G12C-mutant advanced ...

10. lungcancerstoday.com lungcancerstoday.com/post/phase-2-krystal-7-study-first-look-at-efficacy-survival-data-of-adagrasib-plus-pembrolizumab

KRYSTAL-7 Insights: Phase 2 Efficacy, Survival, Safety ... The phase 2 KRYSTAL-7 study demonstrated promising clinical efficacy and a manageable safety profile regardless of PD-L1 status in patients with advanced or ...