Olomorasib for Non-Small Cell Lung Cancer

(SUNRAY-02 Trial)

Recruiting at 320 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

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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to assess if olomorasib in combination with pembrolizumab is more effective than the pembrolizumab and placebo combination in part A in participants with resected KRAS G12C-mutant NSCLC and to assess if olomorasib in combination with durvalumab is more effective than the durvalumab and placebo combination in part B in participants with unresectable KRAS G12C-mutant non-small cell lung cancer. The study may last up to 3 years for each participant.

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.

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

Research shows that drugs targeting the epidermal growth factor receptor (EGFR), like Olomorasib, have improved responses in lung cancers with specific EGFR mutations. Similar drugs, such as osimertinib, have shown significant benefits in patients with advanced non-small cell lung cancer. ^{1 2 3 4 5}

Is Olomorasib safe for humans?

The safety of targeted therapies for non-small cell lung cancer, like Olomorasib, often involves monitoring for side effects such as skin issues, digestive problems, lung issues, and heart problems. While specific safety data for Olomorasib is not detailed, similar treatments have shown these types of side effects, and monitoring protocols are recommended. ^{6 7 8 9 10}

How is the drug Olomorasib different from other treatments for non-small cell lung cancer?

Olomorasib is a novel treatment for non-small cell lung cancer, potentially offering a new mechanism of action compared to existing third-generation drugs like osimertinib, which target specific mutations in the epidermal growth factor receptor (EGFR). While similar drugs focus on inhibiting EGFR mutations, Olomorasib may provide an alternative for patients who develop resistance to current treatments. ^{11 12 13 14 15}

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 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2018]

2. France pubmed.ncbi.nlm.nih.gov

Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. [2022]

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

Biomarkers of Osimertinib Response in Patients with Refractory, EGFR-T790M-positive Non-Small Cell Lung Cancer and Central Nervous System Metastases: The APOLLO Study. [2022]

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

Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study. [2021]

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

Dabrafenib Active in Rare NSCLC Subtype. [2017]

6. Switzerland 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. [2023]

7. England 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. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial. [2020]

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

Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]

10. China 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. [2022]

11. China pubmed.ncbi.nlm.nih.gov

BTN2A1-BRAF fusion may be a novel mechanism of resistance to osimertinib in lung adenocarcinoma: a case report. [2023]

12. France 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. [2022]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of osimertinib for patients with EGFR-mutated NSCLC: a systematic review and meta-analysis of randomized controlled studies. [2022]

15. New Zealand pubmed.ncbi.nlm.nih.gov

Olmutinib: First Global Approval. [2022]