Ramucirumab + Erlotinib for Lung Cancer

(RELAY Trial)

Recruiting at 171 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must be taking: Erlotinib

Must not be taking: CYP3A4 inducers

Disqualifiers: T790M mutation, Brain metastases, 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: 6

545 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination to treat patients with advanced lung cancer who have specific genetic changes. The treatment aims to stop cancer growth by cutting off its blood supply and blocking growth signals. One of the drugs being tested has shown significant survival benefits when combined with other treatments in advanced lung cancer.

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

The trial does not specify if you need to stop all current medications, but you cannot be on ongoing treatment with CYP3A4 inducers or strong inhibitors, or nonsteroidal anti-inflammatory drugs for more than 2 months.

What data supports the effectiveness of the drug combination Ramucirumab and Erlotinib for lung cancer?

Research shows that combining Ramucirumab with Erlotinib improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with EGFR-mutated metastatic non-small cell lung cancer compared to using Erlotinib alone. ^{1 2 3 4 5}

Is the combination of Ramucirumab and Erlotinib safe for lung cancer patients?

The combination of Ramucirumab and Erlotinib has been studied for safety in lung cancer patients, and the safety profile was consistent with what is already known for these drugs. Common side effects include diarrhea, rash, dry skin, nail issues, and fatigue. ^{1 6 7 8 9}

How is the drug combination of Ramucirumab and Erlotinib unique for lung cancer treatment?

The combination of Ramucirumab and Erlotinib is unique because it has been shown to improve progression-free survival (the time during which the cancer does not get worse) in patients with untreated, EGFR-mutated metastatic non-small cell lung cancer, compared to Erlotinib alone. This combination targets specific mutations in cancer cells, potentially offering a more effective treatment option for this type of lung cancer. ^{1 2 8 10 11}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 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 type of advanced lung cancer (Stage IV NSCLC) that has not been treated before and has certain EGFR mutations. Participants must have a life expectancy of at least 3 months, one measurable lesion, and provide tissue samples. It's not for those with certain medical conditions like significant bleeding disorders or recent major blood vessel invasion by cancer.

Inclusion Criteria

You are expected to live for at least 3 more months.

You are able to receive erlotinib as your first treatment if your tumor has certain mutations in the EGFR gene.

You need to provide tissue samples from your lung cancer. If you don't have stage IV lung cancer, other tissue samples may be accepted.

Exclusion Criteria

You have been taking nonsteroidal anti-inflammatory drugs for more than 2 months.

You have a history of coughing up a lot of blood.

There are visible holes inside the tumor on the imaging tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Safety and tolerability of ramucirumab in combination with erlotinib are assessed

Up to 37 months

Every 2 weeks (in-person)

Treatment Part B

Participants receive ramucirumab or placebo in combination with erlotinib

Up to 37 months

Every 2 weeks (in-person)

Treatment Part C

Efficacy and safety of ramucirumab in combination with gefitinib or osimertinib are assessed

Up to 37 months

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 37 months

Treatment Details

Interventions

• Erlotinib
• Gefitinib
• Osimertinib
• Placebo
• Ramucirumab

Trial Overview The study tests the effectiveness and safety of Ramucirumab combined with Erlotinib versus placebo combined with Erlotinib in treating lung cancer. Part C extends to test Ramucirumab with Gefitinib or Osimertinib in East Asian participants based on disease progression and mutation status.

Participant Groups

Group I: Ramucirumab + Gefitinib or Osimertinib Experimental Treatment 3 Interventions

Part C: 10 mg/kg ramucirumab administered every 2 weeks intravenously (IV) + 250 mg Gefitinib or 80 mg Osimertinib daily orally. * Ramucirumab and gefitinib administered during period 1. * Ramucirumab and osimertinib administered during period 2.

Group II: Ramucirumab + Erlotinib Experimental Treatment 2 Interventions

Part A: 10 milligrams per kilogram (mg/kg) ramucirumab administered every 2 weeks intravenously (IV) in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met. Part B: 10 mg/kg ramucirumab administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Group III: Placebo + Erlotinib Placebo Group 2 Interventions

Part B: Placebo administered every 2 weeks IV in combination with 150 mg erlotinib daily orally. Participants may continue to receive treatment until discontinuation criteria are met.

Erlotinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

Approved in United States as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

Approved in Canada as Tarceva for:

• Non-small cell lung cancer
• Pancreatic cancer

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

Findings from Research

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

In the ADAURA study, adjuvant osimertinib significantly improved disease-free survival in patients with resected stage IB to IIIA EGFR-mutated non-small cell lung cancer (NSCLC) compared to placebo, with a median treatment duration of 35.8 months for osimertinib versus 25.1 months for placebo.

After three years of treatment, osimertinib showed no new safety concerns, and patients maintained their health-related quality of life, indicating that osimertinib is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. John, T., Grohé, C., Goldman, JW., et al.[2023]

In the phase 3 RELAY trial, the combination of ramucirumab and erlotinib significantly improved progression-free survival in patients with EGFR-mutated metastatic non-small cell lung cancer (NSCLC), with a median PFS of 19.4 months compared to 12.4 months for the placebo group.

Patient-reported outcomes indicated that overall quality of life and symptom burden were similar between the ramucirumab/erlotinib and placebo/erlotinib groups, although there was a notable increase in reports of blood in sputum for the ramucirumab group, suggesting a specific safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer. Yoh, K., Atagi, S., Reck, M., 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]

In a phase 1b study involving 6 patients with untreated EGFR-mutated non-small cell lung cancer and asymptomatic brain metastases, ramucirumab combined with erlotinib or osimertinib was found to be safe, with no dose-limiting toxicities or serious adverse events related to central nervous system hemorrhage.

The treatment resulted in an objective systemic response in 5 out of 6 patients, and one patient showed a confirmed partial response in the brain, indicating potential efficacy in this challenging patient subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non-small cell lung cancer patients with asymptomatic brain metastases. Kaneda, H., Sawa, K., Daga, H., et al.[2023]

Osimertinib showed a high overall objective response rate (ORR) of 77% in treatment-naïve patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), indicating its efficacy as a first-line treatment.

The median progression-free survival (PFS) was approximately 20.5 months across doses, and no acquired EGFR T790M mutations were detected in post-progression samples, suggesting that osimertinib may effectively manage resistance mechanisms in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. Ramalingam, SS., Yang, JC., Lee, CK., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]

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

RELAY+: Exploratory Study of Ramucirumab Plus Gefitinib in Untreated Patients With EGFR-Mutated Metastatic NSCLC. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]

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

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. [2023]

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

Postprogression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic 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. United States pubmed.ncbi.nlm.nih.gov

Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non-small cell lung cancer patients with asymptomatic brain metastases. [2023]

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

Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small cell lung cancer: exposure-response relationship. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Ramucirumab plus erlotinib versus placebo plus erlotinib in previously untreated EGFR-mutated metastatic non-small-cell lung cancer (RELAY): exploratory analysis of next-generation sequencing results. [2023]