AN OPEN-LABEL, RANDOMIZED, CONTROLLED PHASE 3 STUDY OF SIGVOTATUG VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB COMPARED WITH PEMBROLIZUMAB MONOTHERAPY AS FIRST-LINE TREATMENT IN PARTICIPANTS WITH PD-L1 HIGH (≥50% OF TUMOR CELLS EXPRESSING PD-L1), LOCALLY ADVANCED, UNRESECTABLE, OR METASTATIC NON-SMALL CELL LUNG CANCER (BE6A LUNG-02)

Plain English Summary

This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non-small Cell Lung Cancer With High Levels of PD-L1. is a Phase 3 clinical trial sponsored by Pfizer studying Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC). This trial tests if a new combination of drugs, sigvotatug vedotin plus pembrolizumab, is more effective than pembrolizumab alone for treating advanced non-small cell lung cancer. It is for patients with non-small cell lung cancer that has spread or cannot be removed by surgery, and whose tumors have high levels of a protein called PD-L1. Participants will receive pembrolizumab, and half will also receive sigvotatug vedotin, through IV infusions. Treatment can last up to two years or longer for the combination arm. Standard treatment options for this type of lung cancer include chemotherapy, immunotherapy, targeted therapy, or radiation, depending on specific tumor characteristics and patient health. The trial aims to enroll 714 participants.

Official Summary

The purpose of the study is to compare how the new combination treatment (Sigvotatug Vedotin plus pembrolizumab) works compared to pembrolizumab alone in patients with non-small cell lung cancer (NSCLC) with high levels of PD-L1. This is a protein that acts as a kind of "brake" to keep the body's immune responses under control. The study is seeking for participants who: * Are confirmed to have NSCLC (Stage 3 or 4). * Have PD-L1 levels in more than 50% of the cancer cells. All participants in this study will receive pembrolizumab at the study clinic once every 6 weeks as an intravenous (IV) infusion (give directly into a vein). In addition, half of the participants will also receive Sigvotatug Vedotin once every 2 weeks as an IV infusion in addition to receiving pembrolizumab. Participants may receive pembrolizumab for up to about two years. Those participants taking Sigvotatug Vedotin can continue until their NSCLC is no longer responding. The study team will monitorsee how each participant is doing with the study treatment during regular visits at the clinic.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with Stage IIIB, IIIC, or IV non-small cell lung cancer that cannot be surgically removed or treated with radiation. Tumors must show high levels of PD-L1 (at least 50% of cancer cells). Patients must not have specific genetic mutations (EGFR, ALK, ROS1) that have targeted treatments, and must be eligible for pembrolizumab treatment. Excludes patients with a life expectancy less than 3 months, active brain metastases, recent major surgery, or certain pre-existing conditions like severe lung disease or autoimmune disorders. This trial is studying Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The trial will measure how long patients live (overall survival) and how long their cancer stays under control without getting worse (progression-free survival) to see if the new combination is better The specific primary outcome measures are: Overall Survival (Baseline to date of death from any cause (Approximately 2 years)); Progression Free Survival (PFS) assessed by blinded independent central review (BICR) (From Baseline to to date of first documentation of progression OR death (Approximately 2 year)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a need for more effective first-line treatments for non-small cell lung cancer with high PD-L1 expression, a group that may benefit from novel combination therapies. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-Small Cell Lung Cancer, Carcinoma, Non-Small-Cell Lung, Carcinoma, Non-Small-Cell Lung (NSCLC), where improved treatment options are needed.

Investor Insight

This trial targets a significant market for advanced lung cancer treatments, with pembrolizumab being a key immunotherapy; success could lead to a new combination therapy option, potentially improving Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 714 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your tumor has high PD-L1 levels and if you meet the other eligibility criteria for this trial. Understand that you will receive study drugs via IV infusion at a clinic, requiring regular visits for monitoring and treatment. Be prepared for potential side effects and discuss any new or worsening symptoms with your study team promptly. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 714 participants

Interventions

• DRUG: Sigvotatug Vedotin — MMAE-Antibody Drug Conjugate targeting Integrin Beta-6
• DRUG: Pembrolizumab — Anti-PD-(L)1

Primary Outcomes

• Overall Survival (Baseline to date of death from any cause (Approximately 2 years))
• Progression Free Survival (PFS) assessed by blinded independent central review (BICR) (From Baseline to to date of first documentation of progression OR death (Approximately 2 year))

Secondary Outcomes

• Progression Free Survival as assessed by Investigator (From Baseline to date of first progression or death (Approximately 4 Years))
• Objective Response Rate as assessed by BICR (From Baseline to to the date of progression OR death (approximately to 4 years))
• Objective Response Rate as assessed by Investigator (From Baseline to to the date of progression OR death (approximately to 4 years))
• Duration of Response as assessed by BICR (From the date of the first objective response to the date of disease progression or death (approximately to 4 years))
• Duration of Response as assessed by Investigator (From the date of the first objective response to the date of disease progression or death (approximately to 4 years))

Full Eligibility Criteria

Inclusion Criteria:

1. Participants must meet the following criteria:

   1. Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the AJCC Staging Manual (Version 8.0) and the UICC Staging System (Eighth edition).
   2. Participants with non-squamous histology must have documented negative test results for EGFR, ALK, and ROS1 AGAs and no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies per local standard of care.
   3. Large cell neuroendocrine carcinoma is excluded.
   4. Candidate for treatment with pembrolizumab monotherapy per local guidelines.
2. Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing
3. Measurable disease based on RECIST v1.1 per investigator.
4. Resolution of acute effects of any prior therapy to either baseline severity or NCI CTCAE Grade 1 or less (except for AEs not constituting a safety risk in the investigator's judgment), unless otherwise excluded.

Exclusion Criteria:

1. Life expectancy of \<3 months in the opinion of the investigator.
2. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.
3. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
4. Known or suspected hypersensitivity, intolerance, or contraindication to any excipient contained in the drug formulation of sigvotatug vedotin or pembrolizumab.
5. Participants with any of the following respiratory conditions:

   1. Evidence of noninfectious or drug-induced ILD or pneumonitis
   2. Known DLCO (adjusted for hemoglobin) \<50% predicted.
   3. Grade ≥3 pulmonary disease unrelated to underlying malignancy
6. Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter \<0.5 cm are permitted.
7. Major surgery (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 21 days or minor surgery within 7 days prior to first dose of study intervention.
8. Receipt of a live vaccine within 30 days prior to first dose of study intervention.
9. Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.
10. Uncontrolled diabetes mellitus, defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
11. Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, required a high-dose steroid taper (≥0.5 mg/kg prednisone or equivalent per day) for \>2 weeks, or required treatment with systemic immunosuppressive therapy.
12. History of autoimmune disease that has required systemic treatment in the past 2 years
13. Participants with prior solid organ or bone marrow transplantation.
14. Currently receiving a high-dose steroid (\>10 mg prednisone or equivalent per day) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant.
15. Prior and concomitant therapy:

    1. Any prior treatment with MMAE-derived drugs or IB6 targeting agents.
    2. Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.

       * (Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose.
       * Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose.
    3. Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.
    4. Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.
    5. Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor
16. History of or current ongoing infection, including participants positive for active HIV, HBV, or HCV.
17. Severe uncontrolled cardiac or cerebrovascular condition within the previous 6 months

Trial Locations

• Providence St. Jude Medical Center Virginia K. Crosson Cancer Center and Infusion Center, Fullerton, California, United States
• Providence St. Jude Medical Center, Fullerton, California, United States
• St. Jude Heritage Medical Group - Fullerton Plaza Multi-Specialty Clinic (Pulmonary Function Test), Fullerton, California, United States
• Intermountain Health Cancer Center Lutheran Hospital, Golden, Colorado, United States
• Cancer Centers of Colorado St. Mary's Regional Hospital, Grand Junction, Colorado, United States
• Intermountain Health St. Mary's Regional Hospital, Grand Junction, Colorado, United States
• Intermountain Health, Grand Junction, Colorado, United States
• Intermountain Health Lutheran Hospital, Wheat Ridge, Colorado, United States
• Washington DC Veterans Affairs Medical Center, Washington D.C., District of Columbia, United States
• Mid Florida Hematology and Oncology Center, Orange City, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Lung Cancer
• Metastatic Lung Cancer
• Advanced Lung Cancer
• Carcinoma
• Oncology
• Immunotherapy
• Targeted Therapy
• Cancer
• Tumor

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