Olomorasib for Non-Small Cell Lung Cancer

(SUNRAY-02 Trial)

Recruiting at 426 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

Disqualifiers: EGFR, ALK, Cancer, Autoimmune, 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

Duration: 3 years

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new drug olomorasib, combined with pembrolizumab or durvalumab, can more effectively treat non-small cell lung cancer (NSCLC) than the standard treatment. It specifically targets NSCLC with a KRAS G12C mutation, a gene change present in some lung cancers. The trial seeks participants whose lung cancer has this mutation and who meet certain conditions, such as having undergone specific prior treatments. Participants will take olomorasib with either pembrolizumab or durvalumab to assess if this combination outperforms current options. Ideal candidates have a confirmed KRAS G12C mutation in their lung cancer and have tried prescribed treatments that haven't fully succeeded. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it is important to discuss your current medications with the trial team to ensure there are no conflicts.

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

Research has shown that olomorasib, when combined with pembrolizumab, is generally safe. In studies, patients with a specific lung cancer mutation (KRAS G12C) tolerated this treatment well. Serious side effects were rare, and the combination effectively fought cancer.

For olomorasib combined with durvalumab, less detailed information is available. However, since olomorasib is in the final stages of testing, earlier trials likely demonstrated sufficient safety to proceed. This combination remains under study, and its safety will continue to be closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about olomorasib for non-small cell lung cancer because it targets the KRAS mutation, a common driver in many lung cancers, which is different from the mechanisms of standard treatments like chemotherapy or immune checkpoint inhibitors. Olomorasib stands out by being combined with pembrolizumab or durvalumab, potentially enhancing the immune system's ability to fight cancer cells. This combination could offer a more targeted approach, potentially leading to more effective and personalized treatment options compared to traditional therapies that often have broader effects.

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

Research has shown that combining the drugs olomorasib and pembrolizumab, which participants in this trial may receive, may help treat KRAS G12C-mutant non-small cell lung cancer (NSCLC). In studies, this combination shrank tumors in 74% of patients and prevented cancer growth or spread in 91% of patients. Additionally, early results suggest that olomorasib, when used with durvalumab, might effectively treat NSCLC that cannot be surgically removed. These findings offer hope for people with this type of lung cancer. ^{1 2 3 4 5}

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 people with a specific mutation in their lung cancer (KRAS G12C). Part A includes those who've had surgery to remove the cancer, while Part B is for those whose cancer can't be removed by surgery. Participants must meet other health requirements not specified here.

Inclusion Criteria

Contraceptive use should be consistent with local regulations for those participating in clinical studies

I can take pills by mouth.

My lung cancer diagnosis was confirmed through lab tests.

Exclusion Criteria

I have another cancer that is getting worse or was treated in the last 3 years.

I have been treated for an autoimmune disease within the last 2 years, except for hormone replacement.

I've had a severe reaction to immunotherapy or an unresolved mild reaction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olomorasib in combination with pembrolizumab or durvalumab for up to 1 year, followed by olomorasib or placebo alone for up to 3 years

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Olomorasib
• Pembrolizumab

Trial Overview The study tests if Olomorasib combined with Pembrolizumab (Part A) or Durvalumab (Part B) works better than these immunotherapies alone with a placebo. It's a comparison over up to three years per participant to see which combination offers more benefits.

How Is the Trial Designed?

Group I: Part B: Olomorasib + Durvalumab Experimental Treatment 2 Interventions

Participants will receive olomorasib administered orally in combination with durvalumab administered IV for up to 1 year followed by olomorasib alone for up to 3 years of total treatment.

Group II: Part A: Olomorasib + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive olomorasib administered orally in combination with pembrolizumab intravenously (IV) for up to 1 year followed by olomorasib alone for up to 3 years of total treatment.

Group III: Part B: Placebo + Durvalumab Placebo Group 2 Interventions

Participants will receive placebo administered orally in combination with durvalumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment.

Group IV: Part A: Placebo + Pembrolizumab Placebo Group 2 Interventions

Participants will receive placebo administered orally in combination with pembrolizumab administered IV for up to 1 year followed by placebo alone for up to 3 years of total treatment.

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

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

The case study highlights that the acquisition of a BTN2A1-BRAF fusion may be a mechanism of acquired resistance to osimertinib in a patient with non-small cell lung cancer (NSCLC), suggesting that resistance can develop through genetic changes after initial treatment.

Despite the presence of PD-L1 expression, switching to the PD-L1 inhibitor duvalizumab did not yield significant improvements, indicating that patients with sensitive EGFR mutations may not benefit from PD-L1 inhibitors, regardless of PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTN2A1-BRAF fusion may be a novel mechanism of resistance to osimertinib in lung adenocarcinoma: a case report. Kong, WM., Guo, YJ., Ma, J., et al.[2023]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

Icotinib showed a 34.2% overall objective response rate and a 75.0% disease control rate in 76 patients with advanced nonsquamous non-small cell lung cancer who had unknown EGFR mutation status and had not responded to second-line chemotherapy.

The treatment resulted in a median progression-free survival of 11.0 months and a median overall survival of 16.9 months, indicating that icotinib is an effective option for these patients, with tolerable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of icotinib in patients with advanced nonsquamous non-small cell lung cancer with unknown EGFR mutation status that failed to respond to second-line chemotherapy. Xu, L., Xu, XH., Yuan, C., et al.[2022]

In vitro studies identified the BRAF G469A mutation as a key mechanism of acquired resistance to osimertinib in non-small cell lung cancer cells, indicating that this mutation allows cancer cells to continue growing despite treatment.

Treatment with selumetinib and trametinib was effective in restoring sensitivity to osimertinib and increasing cell death in resistant clones, suggesting potential strategies to overcome resistance in patients with this mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired BRAF G469A Mutation as a Resistance Mechanism to First-Line Osimertinib Treatment in NSCLC Cell Lines Harboring an EGFR Exon 19 Deletion. La Monica, S., Minari, R., Cretella, D., et al.[2022]

CT-guided core-needle biopsy is a safe and effective method for obtaining tissue samples from patients with advanced non-small-cell lung cancer (NSCLC) for EGFR gene mutation analysis, with no life-threatening complications reported in the study of 17 patients.

In this study, 70.6% of patients had EGFR gene mutations, and those with mutations showed a significantly higher response rate (91.7%) to the EGFR inhibitor gefitinib compared to nonmutants, who had a 0% response rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography-guided core-needle biopsy specimens demonstrate epidermal growth factor receptor mutations in patients with non-small-cell lung cancer. Chen, CM., Chang, JW., Cheung, YC., et al.[2018]

In the FLAURA China study involving 136 patients with EGFR mutation-positive advanced non-small-cell lung cancer, first-line treatment with osimertinib significantly improved progression-free survival (PFS) by 8 months compared to comparator EGFR TKIs, with median PFS of 17.8 months versus 9.8 months.

Osimertinib also showed a trend towards improved overall survival (OS) with a median of 33.1 months compared to 25.7 months for the comparator group, while the safety profile was consistent with previous findings, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Cheng, Y., He, Y., Li, W., et al.[2022]

A study of 130 treatment courses in 111 patients revealed that safety monitoring activities (SMAs) for EGFR and ALK inhibitors were inconsistently conducted, with prevalence ranging from 10.0% to 84.6%, and 31.5% of courses had no SMAs performed.

EGFR inhibitors were associated with a higher likelihood of SMAs being conducted compared to ALK inhibitors, highlighting the need for clinicians to closely follow FDA guidelines to ensure patient safety and monitor for serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. Singh, AM., Rubiera-Pebe, R., Ahmad, Y., et al.[2023]

Dabrafenib, a BRAF inhibitor, shows significant effectiveness as a single-agent treatment for patients with advanced non-small cell lung cancer that has the BRAF V600E mutation, indicating its potential as a targeted therapy.

Combining dabrafenib with a MEK inhibitor may enhance treatment efficacy, suggesting that a combination therapy approach could be more beneficial for these patients than using dabrafenib alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib Active in Rare NSCLC Subtype. [2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06890598

NCT06890598 | Study of Olomorasib (LY3537982) in ... The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425020751

P3.18.09 SUNRAY-02: A Phase 3 Study of Olomorasib and ... The phase 1/2 LOXO-RAS-20001 study (NCT04956640) showed that olomorasib alone and in combination with pembrolizumab demonstrated promising preliminary efficacy ...

3. trials.lilly.com trials.lilly.com/en-US/trial/585993

Study of Olomorasib (LY3537982) in Combination ... - Lilly Trials The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination.

4. 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 ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/585993

Study of Olomorasib (LY3537982) in Combination With ... The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination ...