Sigvotatug Vedotin + Pembrolizumab for Non-Small Cell Lung Cancer

(Be6A Lung-02 Trial)

Recruiting at 160 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Pembrolizumab

Must not be taking: High-dose steroids, Immunosuppressants

Disqualifiers: Other malignancy, Respiratory conditions, 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 2 years

714 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new combination of treatments outperforms the standard treatment for individuals with advanced non-small cell lung cancer (NSCLC). It compares the effectiveness of Sigvotatug Vedotin (an experimental treatment) combined with pembrolizumab against pembrolizumab alone. The study targets participants whose cancer cells exhibit high levels of PD-L1, a protein influencing immune response. Individuals with Stage 3 or 4 NSCLC and more than 50% PD-L1 in their cancer cells may qualify for this trial. Participants will receive pembrolizumab, and some will also receive Sigvotatug Vedotin, with regular clinic visits to monitor progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on high-dose steroids or certain immune suppressants, you may need to adjust your treatment. It's best to discuss your specific medications with the study team.

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

Research shows that sigvotatug vedotin has promising results for treating non-small cell lung cancer (NSCLC). It has a manageable safety profile, meaning that while side effects exist, they are generally acceptable and controllable.

Patients have taken sigvotatug vedotin with pembrolizumab, another cancer treatment. Tests have shown that this combination is generally well-tolerated, meaning most people can handle the side effects. However, sigvotatug vedotin is still under study, so not all safety details are fully understood yet.

Pembrolizumab is already approved for other conditions, indicating a known safety record from previous studies and use. However, like any treatment, it can have side effects, which are carefully monitored during the trial.

Participants in the study will receive regular check-ups to ensure their safety and manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sigvotatug Vedotin combined with Pembrolizumab for treating non-small cell lung cancer because it offers a fresh approach compared to standard treatments like chemotherapy or traditional immunotherapy. Sigvotatug Vedotin is unique because it's an antibody-drug conjugate, meaning it delivers a powerful anti-cancer drug directly into the cancer cells, reducing damage to healthy cells. Pairing this with Pembrolizumab, an already established immune checkpoint inhibitor, could enhance the immune system's ability to fight cancer more effectively. This combination could potentially improve outcomes for patients by targeting cancer cells more precisely and boosting the body's immune response.

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

This trial will compare the combination of Sigvotatug Vedotin with pembrolizumab to pembrolizumab monotherapy for treating non-small cell lung cancer (NSCLC). Studies have shown that using Sigvotatug Vedotin with pembrolizumab holds promise, with research indicating a confirmed overall response rate (ORR) of 42.9% in patients with high PD-L1 levels. Nearly half of these patients experienced cancer shrinkage or disappearance. Pembrolizumab alone is already effective for NSCLC, particularly in patients with high PD-L1. Adding Sigvotatug Vedotin, which targets a specific protein on cancer cells, may enhance the treatment's effectiveness. These early results suggest that this combination could be a strong option for managing advanced lung cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for people with advanced non-small cell lung cancer (NSCLC) who can't have surgery or chemoradiation. They must not have certain genetic mutations, small cell elements, or large cell neuroendocrine carcinoma. Their tumors should express PD-L1 in at least 50% of cells and they should be candidates for pembrolizumab treatment.

Inclusion Criteria

My tumor shows high PD-L1 levels.

Participants must have measurable disease based on RECIST v1.1 per investigator

My lung cancer is at an advanced stage and surgery or definitive chemoradiation is not an option for me.

Exclusion Criteria

Participants must have a life expectancy of <3 months in the opinion of the investigator

Participants must not have 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

Participants with prior solid organ or bone marrow transplantation are excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 6 weeks and Sigvotatug Vedotin every 2 weeks as IV infusions

Up to 2 years

Regular visits at the clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue receiving Sigvotatug Vedotin until NSCLC is no longer responding

Until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sigvotatug Vedotin

Trial Overview The study compares a new combination therapy (Sigvotatug Vedotin plus pembrolizumab) to just pembrolizumab alone in patients with high levels of PD-L1. Participants will receive treatments via IV infusions at the clinic, with regular monitoring by the study team.

How Is the Trial Designed?

Group I: Sigvotatug Vedotin with Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive Sigvotatug Vedotin, administered as an IV infusion and pembrolizumab, administered as an IV infusion.

Group II: Pembrolizumab Monotherapy Active Control 1 Intervention

Participants will receive pembrolizumab, administered as an IV infusion.

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

The study confirms that PD-1 inhibitors like Pembrolizumab and Nivolumab improve response and survival rates in advanced melanoma patients, especially when combined with the CTLA-4 inhibitor Ipilimumab, which shows superior efficacy compared to monotherapies.

However, these immunotherapies are associated with significant immune-related adverse events, some of which can be life-threatening, highlighting the need for further studies to better understand their safety profiles and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. Schaefer, A., Sachpekidis, C., Diella, F., et al.[2020]

Pembrolizumab, an anti-PD-1 antibody, is effective as a first-line treatment for advanced nonsmall cell lung cancer (NSCLC) in patients with high PD-L1 expression (≥50%) and as a second-line option for those with lower PD-L1 expression (≥1%).

When combined with standard chemotherapy, pembrolizumab has demonstrated superior clinical outcomes compared to chemotherapy alone in patients with advanced NSCLC without targetable mutations, regardless of their PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of nonsmall cell lung cancer: Current status and future directions. Qin, Q., Li, B.[2020]

Citations

1. onclive.com onclive.com/view/novel-adc-sigvotatug-vedotin-generates-early-efficacy-in-nsclc

Novel ADC Sigvotatug Vedotin Generates Early Efficacy in ... Additional findings presented at the 2025 ASCO Annual Meeting illustrated a confirmed ORR of 42.9% (95% CI, 21.8%-66.0%) when pembrolizumab was ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06758401

NCT06758401 | This is a Study to Learn About ... The purpose of the study is to compare how the new combination treatment (Sigvotatug Vedotin plus pembrolizumab) works compared to pembrolizumab alone in ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8521

Efficacy and safety of sigvotatug vedotin, an investigational ... Conclusions: SV continues to demonstrate encouraging antitumor activity and a manageable safety profile in pts with NSCLC. Data at 1.8 mg/kg ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT483586

Sigvotatug vedotin (SV), an investigational integrin beta-6 ... Real-world comparative effectiveness and safety of pembrolizumab vs chemotherapy for previously untreated PD-L1≥50% metastatic non-small cell lung cancer.

5. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/NCT06758401

Sigvotatug vedotin AN OPEN-LABEL, RANDOMIZED, CONTROLLED PHASE 3 STUDY OF SIGVOTATUG VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB COMPARED WITH PEMBROLIZUMAB MONOTHERAPY AS FIRST- ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT441304

Efficacy and safety of sigvotatug vedotin, an investigational ... Conclusions: SV continues to demonstrate encouraging antitumor activity and a manageable safety profile in pts with NSCLC. Data at 1.8 mg/kg AiBW 2Q4W support ...

7. onclive.com onclive.com/view/dr-sanborn-on-early-efficacy-and-safety-data-with-sigvotatug-vedotin-plus-pembrolizumab-in-nsclc

Dr Sanborn on Early Efficacy and Safety Data With ... Rachel E. Sanborn, MD, discusses preclinical and early clinical data supporting the use of the IB6-directed ADC sigvotatug vedotin in ...