SGN-B7H4V for Advanced Cancers

No longer recruiting at 45 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Corticosteroids, MMAE agents

Disqualifiers: Other malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and side effects of the drug Felmetatug Vedotin (SGN-B7H4V), both alone and in combination with pembrolizumab, for individuals with advanced solid tumors. It will assess the effectiveness of these treatments for various cancers, such as certain breast and lung cancers, particularly when the cancer is inoperable or has metastasized. Suitable candidates for this trial may include those whose cancer has returned despite standard treatments or who cannot tolerate them. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it is common for clinical trials to have specific requirements, so it's best to discuss your current medications with the trial coordinators.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that Felmetatug Vedotin is still undergoing safety testing in people with advanced cancers. Current studies focus on how well participants tolerate the treatment and what side effects might occur. However, specific safety details and information about side effects are not yet available.

Researchers are testing Felmetatug Vedotin both alone and with pembrolizumab. Pembrolizumab is already approved for use in other cancers, indicating its relative safety on its own. However, the safety of these two drugs when used together is still under investigation.

As this study is in its early stages, it primarily aims to find safe dosage levels and identify possible side effects. More detailed safety information will likely emerge as research progresses. For now, joining the trial requires understanding that the treatment's safety details are still being developed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Felmetatug Vedotin is unique because it targets cancer cells differently than traditional chemotherapy. Unlike standard treatments that attack both cancerous and healthy cells, Felmetatug Vedotin acts specifically on tumor cells by binding to the B7-H4 protein, which is often overexpressed in certain advanced cancers. This targeted approach aims to minimize damage to healthy cells, potentially leading to fewer side effects. Additionally, when combined with Pembrolizumab, an immunotherapy drug, it may enhance the immune system's ability to fight cancer, offering a promising two-pronged attack on tumors. Researchers are excited about these treatments because they could provide more effective and tolerable options for patients with advanced cancers.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that Felmetatug Vedotin targets a protein called B7-H4 on some cancer cells, allowing the drug to enter and destroy them. In this trial, some participants will receive Felmetatug Vedotin as monotherapy. Other studies have reported that about 18.5% of patients experienced tumor shrinkage after taking Felmetatug Vedotin. Other participants in this trial will receive Felmetatug Vedotin combined with pembrolizumab, which boosts the immune system to fight cancer. Early results suggest this combination might enhance treatment effectiveness. While these findings are promising, further research is needed to confirm the treatments' effectiveness for different cancer types. ^{1 2 6 7 8}

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 adults with advanced solid tumors that are locally advanced, unresectable, or metastatic. Participants must be in good physical condition (ECOG 0 or 1), have measurable disease, and provide tumor tissue. Those with recent other cancers, brain metastases, previous similar treatments, significant neuropathy, or active corneal disease can't join.

Inclusion Criteria

My condition has not improved with standard treatments or I cannot tolerate them.

I have a specific type of advanced or metastatic cancer.

I can provide a sample of my tumor for the study.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

My brain metastases are stable, and I haven't taken corticosteroids for them in the last 7 days.

I have not had any other cancers in the last 3 years, or if I have, they are not likely to spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A and B

Determine the appropriate dosage of Felmetatug Vedotin for participants

8-12 weeks

Treatment Part C

Evaluate the safety and efficacy of Felmetatug Vedotin in treating solid tumor cancers

12-16 weeks

Treatment Part D

Determine the dosage of Felmetatug Vedotin in combination with pembrolizumab

8-12 weeks

Treatment Part E

Evaluate the safety and efficacy of Felmetatug Vedotin with pembrolizumab in treating triple negative breast cancer

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• SGN-B7H4V

Trial Overview SGN-B7H4V is being tested for safety and effectiveness in treating various solid tumors. The study has three parts: determining the right dose (Parts A & B) and then assessing its safety and how well it works at that dose (Part C).

How Is the Trial Designed?

Group I: Felmetatug Vedotin and Pembrolizumab (Parts D and E) Experimental Treatment 2 Interventions

Felmetatug Vedotin in combination with Pembrolizumab.

Group II: Felmetatug Vedotin (Parts A, B, and C) Experimental Treatment 1 Intervention

Felmetatug Vedotin monotherapy

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

B7-H4, a member of the B7 superfamily, is known to negatively regulate T cell responses and is often overexpressed in tumors, serving as a negative prognostic marker for various cancers.

Contrary to its expected role, recent findings suggest that B7-H4 actually inhibits tumor growth and is necessary for promoting effective antitumor responses, indicating a complex role in cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H4 is a positive regulator of antitumor immunity. Rahbar, R., Ohashi, PS.[2022]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

In a study of 408 head and neck squamous cell carcinoma (HNSCC) samples, strong expression of the protein B7-H3 was linked to better overall survival, particularly in patients with p16-negative oropharyngeal SCC, suggesting a potential protective role.

Conversely, the expression of B7-H4 and mRNA levels of both B7-H3 and B7-H4 did not show significant associations with patient survival, indicating that B7-H3 may have a unique prognostic value in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic impact of B7-H3 and B7-H4 in head and neck squamous cell carcinoma. Borgmann, M., Oetting, A., Meyer, F., et al.[2023]

B7-H4 is identified as a promising therapeutic target in cancer treatment due to its high expression in various tumors, which correlates with more aggressive disease and poorer clinical outcomes.

Blocking B7-H4 may enhance anti-tumor immune responses by reducing the suppression of CD4+ T-cell activity and altering the tumor microenvironment, potentially leading to better clearance of tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential targeting of B7-H4 for the treatment of cancer. Podojil, JR., Miller, SD.[2022]

A specific antibody was isolated from ovarian cancer patients that can effectively bind to B7-H4, an immune checkpoint that inhibits T-cell responses, potentially enhancing antitumor immunity.

The study utilized a yeast-display library to identify functional antibody fragments that can counteract B7-H4's inhibitory effects, suggesting a promising therapeutic approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and Validation of Anti-B7-H4 scFvs from an Ovarian Cancer scFv Yeast-Display Library. Dangaj, D., Scholler, N.[2015]

VX15/2503 was well tolerated in a study of 42 patients with advanced solid tumors, with most side effects being mild (grade 1 or 2), such as nausea and fatigue, indicating a favorable safety profile.

The treatment showed promising antitumor activity, with one patient achieving a partial response and 45.2% of patients maintaining stable disease for at least 8 weeks, suggesting that VX15/2503 may enhance immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. Patnaik, A., Weiss, GJ., Leonard, JE., et al.[2022]

The maximum tolerated dose (MTD) of BMS-690514, when combined with paclitaxel and carboplatin, was determined to be 150 mg/day, with manageable side effects such as diarrhea and thrombosis.

The treatment showed promising antitumor activity, with 12 partial responses observed among 32 evaluable patients, including notable responses in non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies. Chow, LQ., Jonker, DI., Dy, GK., et al.[2015]

Bevacizumab treatment in a mouse model of malignant glioma led to increased survival and significantly reduced tumor size and invasion compared to control, indicating its efficacy in managing glioblastoma.

BMP4 also reduced tumor invasion independently but did not improve survival or show a synergistic effect when combined with bevacizumab, suggesting it has a separate beneficial role in glioblastoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma. Rahman, M., Azari, H., Deleyrolle, L., et al.[2015]

B7-H4 is expressed on primary ovarian cancer cells and tumor-associated macrophages in vivo, but is quickly lost in established cell lines, indicating its potential role in immune evasion by tumors.

Antibodies targeting B7-H4 can reverse the inhibition of T-cell activation caused by B7-H4+ tumor cells, suggesting that blocking B7-H4 interactions may be an effective therapeutic strategy for enhancing antitumor immune responses in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel recombinant human b7-h4 antibodies overcome tumoral immune escape to potentiate T-cell antitumor responses. Dangaj, D., Lanitis, E., Zhao, A., et al.[2022]

The combination of nivolumab and erlotinib was found to be tolerable in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), with treatment-related grade 3 toxicities occurring in only five out of twenty patients, and no severe grade 4 toxicities reported.

Among the TKI-treated patients, the objective response rate was 15%, with some patients experiencing durable responses lasting up to 38.2 months, indicating potential efficacy of this combination therapy in managing advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Gettinger, S., Hellmann, MD., Chow, LQM., et al.[2019]

Patients with gastric cancer had significantly higher levels of soluble B7-H4 (sB7-H4) in their blood compared to healthy individuals, indicating its potential role as a biomarker for the disease.

Higher levels of sB7-H4 were associated with worse clinical outcomes, including larger tumor size and lower overall survival rates, suggesting that sB7-H4 could be a valuable marker for predicting cancer progression and patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer. Shi, H., Ji, M., Wu, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05194072

A Study of Felmetatug Vedotin/SGN-B7H4V in Advanced ... The purpose of the study is to test the safety of the medicine called Felmetatug Vedotin alone and with pembrolizumab in participants with solid tumors.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985252/

B7 Homolog 4 (B7-H4)-Directed Agents in Oncology ... To date, 11 different B7-H4–directed agents have entered at least 16 clinical trials for patients with solid tumor cancers. These agents, ...

3. withpower.com withpower.com/trial/phase-1-carcinoma-2022-68790

SGN-B7H4V for Advanced Cancers · Info for Participants This indicates that drugs like SGN-B7H4V, which target B7-H4, may be effective in treating cancers by enhancing the body's immune response against tumor cells.

4. researchgate.net researchgate.net/publication/390669503_B7_Homolog_4_B7-H4-Directed_Agents_in_Oncology_Clinical_Trials_A_Review

(PDF) B7 Homolog 4 (B7-H4)-Directed Agents in Oncology ... This review highlights the current landscape of B7-H4–targeted agents, their progress in clinical trials, and the potential for combination approaches.

5. nature.com nature.com/articles/s41698-025-01011-7

Immune-checkpoint targeting drug conjugates: a novel ... The phase I study SGNB7H4V-001 (NCT05194072) is evaluating felmetatug vedotin in refractory advanced solid tumors irrespective of B7-H4 ...

6. adcreview.com adcreview.com/drugmap/felmetatug-vedotin-pf-08046048-sgn-b7h4v/

Felmetatug Vedotin | PF-08046048 | SGN-B7H4V The purpose of the study is to test the safety of the medicine called SGN-B7H4V alone and with pembrolizumab in participants with solid tumors.

7. delta.larvol.com delta.larvol.com/Products/?ProductId=843ef728-5491-4ff0-bdd3-ccbff737a027

felmetatug vedotin (PF-08046048) / Pfizer Felmetatug vedotin (SGN-B7H4V), and GSK5733584, have demonstrated early clinical activity with promising response rates in triple-negative breast cancer (TNBC).

8. prnewswire.com prnewswire.com/news-releases/b7-h4-targeting-therapies-market-growth-set-to-accelerate-across-the-7mm-during-the-study-period-20252040-with-advances-in-immunotherapy--delveinsight-302512874.html

B7-H4 Targeting Therapies Market Growth Set to ... Felmetatug vedotin is currently in Phase I clinical trials for the treatment of advanced solid tumors such as ovarian, peritoneal, and triple- ...