Rilvegostomig + Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 272 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Anticonvulsants, Anti-PD-1, others

Disqualifiers: Small cell, Brain metastases, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 5 years

878 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for non-small cell lung cancer (NSCLC), focusing on their effectiveness and safety. It compares rilvegostomig (an experimental treatment) and pembrolizumab (KEYTRUDA), both combined with chemotherapy, to determine the better first treatment option. People with stage IV non-squamous NSCLC, whose tumors have tested positive for a specific protein (PD-L1), might be suitable candidates. The trial aims to identify which combination more effectively treats this type of lung cancer. As a Phase 3 trial, it represents the final step before FDA approval, offering patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on steroids or other immunosuppressive treatments for autoimmune or inflammatory disorders, you may need to stop them, as these are part of the exclusion criteria.

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

Research has shown that rilvegostomig, which aids the immune system in fighting cancer by targeting specific proteins, has a good safety record. In earlier studies, most patients tolerated it well, experiencing only mild to moderate side effects. Serious reactions were rare, indicating that rilvegostomig is generally safe for people.

Pembrolizumab has already received approval for some cancers, so its safety profile is well-known. Patients have experienced side effects like tiredness and nausea, but these are usually not severe.

Both treatments are currently being tested with chemotherapy to assess their combined effectiveness. Overall, current evidence suggests that both rilvegostomig and pembrolizumab are safe options for those considering participation in this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Rilvegostomig for non-small cell lung cancer because it offers a new approach by targeting specific pathways involved in cancer growth. Unlike standard treatments such as chemotherapy or pembrolizumab alone, Rilvegostomig is designed to enhance the immune system's response to cancer cells, potentially leading to better outcomes. This novel mechanism, combined with its use alongside existing therapies, might improve efficacy and provide a more comprehensive treatment strategy for patients battling this type of lung cancer.

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

This trial will compare two treatment arms for non-small cell lung cancer. In Arm A, participants will receive Rilvegostomig with platinum-based doublet chemotherapy, followed by Rilvegostomig monotherapy plus pemetrexed for maintenance. Studies have shown that Rilvegostomig targets two specific parts of the immune system, PD-1 and TIGIT, which usually prevent the immune system from attacking cancer cells. Early data suggests that Rilvegostomig can activate T cells, a type of immune cell, to help them fight tumors in patients with advanced or spreading non-small cell lung cancer (NSCLC). Initial results have been promising, showing early signs of fighting cancer and being safe for patients who have already tried standard treatments.

In Arm B, participants will receive Pembrolizumab with platinum-based doublet chemotherapy, followed by Pembrolizumab monotherapy plus pemetrexed for maintenance. Pembrolizumab has proven effective for treating certain cancers, including metastatic non-small cell lung cancer. Research shows that when combined with chemotherapy, it boosts the body's immune response against cancer cells, leading to better outcomes for many patients. These findings suggest that both treatments have potential, but Rilvegostomig is still under study to confirm its effectiveness. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-squamous non-small cell lung cancer (NSCLC) that has spread, and whose tumors show PD-L1 expression. Participants must be new to treatment for metastatic NSCLC.

Inclusion Criteria

My lung cancer is at stage IV and cannot be cured with treatment.

My cancer does not have EGFR, ALK, ROS1 mutations, or other specific gene changes.

My organs and bone marrow are working well.

Exclusion Criteria

I have an active tuberculosis infection.

I am on long-term steroids for an autoimmune or inflammatory condition.

My cancer has small cell and neuroendocrine features.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rilvegostomig or pembrolizumab in combination with platinum-based doublet chemotherapy

Up to approximately 5 years

Maintenance

Participants receive rilvegostomig or pembrolizumab monotherapy plus pemetrexed

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Rilvegostomig

Trial Overview The study compares the effectiveness of two drugs, Rilvegostomig and Pembrolizumab, each paired with chemotherapy (Pemetrexed plus either Carboplatin or Cisplatin), in treating advanced NSCLC.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 4 Interventions

Rilvegostomig in combination with platinum-based doublet chemotherapy followed by rilvegostomig monotherapy plus pemetrexed in maintenance.

Group II: Arm B Active Control 4 Interventions

Pembrolizumab in combination with platinum-based doublet chemotherapy followed by pembrolizumab monotherapy plus pemetrexed in maintenance.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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 (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]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., 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 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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04995523

NCT04995523 | A Study of AZD2936 Anti-TIGIT/Anti-PD-1 ... This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03314-8/fulltext

1446P Preliminary efficacy and safety of rilvegostomig ... Rilvegostomig is a bispecific, humanised IgG1 targeting PD-1 and TIGIT, receptors that suppress antitumour T cell activity. Initial data from the first-in-human ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8521

First-line (1L) datopotamab deruxtecan (Dato-DXd) + ... Dato-DXd + rilvegostomig had encouraging activity as 1L treatment for pts with a/mNSCLC without AGAs, with responses seen in both histologies and across all PD ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7020C00001

A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific ... This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT400910

Safety, pharmacokinetics (PK), pharmacodynamics ( ... AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D702BC00001

A Global Phase III Study of Rilvegostomig or ... This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab.