SGN-B6A for Cancer

Recruiting at 191 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Corticosteroids, MMAE agents

Disqualifiers: CNS metastases, Neuropathy, ILD, others

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

Compensation: Varies

Number of Visits: Unknown

1006 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called sigvotatug vedotin (SGN-B6A) to determine its safety and effectiveness in treating solid tumors. Researchers will study it alone and in combination with other drugs like pembrolizumab and chemotherapy to identify potential side effects and assess its efficacy across different cancer types. Suitable candidates for this trial include individuals with certain solid tumors, such as non-small cell lung cancer or head and neck cancer, particularly if previous treatments have failed or if they have not yet begun treatment. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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

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

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

Research has shown that sigvotatug vedotin, alone or with pembrolizumab, has a manageable safety profile for patients with certain cancers, such as non-small cell lung cancer (NSCLC). While side effects occur, they are usually not severe and can be controlled.

In studies, patients taking sigvotatug vedotin at a dose of 1.8 mg/kg experienced side effects, yet the treatment maintained a manageable safety profile. When combined with pembrolizumab, the treatment demonstrated promising anti-cancer effects and was generally well-tolerated.

This trial is in its early stages, focusing on determining the right dose and closely monitoring any side effects. This phase is crucial for understanding the treatment's safety and tolerability for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sigvotatug vedotin because it offers a novel approach to treating cancers like non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and esophageal squamous cell carcinoma (ESCC). Unlike traditional chemotherapy, which targets all rapidly dividing cells, sigvotatug vedotin is an antibody-drug conjugate that specifically targets cancer cells, potentially minimizing damage to healthy cells. It combines with pembrolizumab, an immunotherapy, to enhance the body's immune response against cancer. This combination could result in more effective and targeted cancer treatment, offering hope for improved outcomes with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that sigvotatug vedotin, also known as SGN-B6A, may help treat solid tumors. In studies, this drug shrank tumors in nearly one in five patients with non-small cell lung cancer (NSCLC). In this trial, some participants will receive sigvotatug vedotin combined with pembrolizumab, a drug that boosts the immune system. Together, the success rate increased to about 43%, suggesting the combination might be more effective. Sigvotatug vedotin targets a protein called integrin beta-6, delivering the cancer-fighting drug directly to the tumor, potentially reducing its size. These early results are promising in the fight against certain solid tumors. ^{1 4 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 adults with certain advanced solid tumors, including esophageal, breast, lung cancers and more. Participants must have relapsed or be intolerant to standard treatments. They should not have received prior therapies that caused severe immune reactions and must not have active brain metastases or serious infections.

Inclusion Criteria

My cancer is confirmed to be advanced and cannot be removed by surgery.

I am fully active or restricted in physically strenuous activity but can do light work.

My tumor can be biopsied, and I agree to undergo this procedure.

Exclusion Criteria

My lung's ability to transfer gas is less than half of what's expected.

I stopped a treatment because of a severe immune reaction.

I haven't had a severe infection in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Determine the appropriate dose of sigvotatug vedotin for participants

8 weeks

Dose Expansion (Part B)

Evaluate the safety and efficacy of the determined dose of sigvotatug vedotin

12 weeks

Combination Therapy (Parts C and D)

Assess the safety and efficacy of sigvotatug vedotin in combination with pembrolizumab and/or chemotherapy

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• SGN-B6A

Trial Overview SGN-B6A alone and in combination with pembrolizumab, with or without chemotherapy drugs cisplatin or carboplatin, is being tested across four parts of the study to determine safety and effectiveness in treating various solid tumors.

How Is the Trial Designed?

Group I: Part D: sigvotatug vedotin combination therapy in 1L NSCLC Experimental Treatment 3 Interventions

sigvotatug vedotin + pembrolizumab +/- (carboplatin)

Group II: Part D: sigvotatug vedotin combination therapy in 1L HNSCC Experimental Treatment 4 Interventions

sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)

Group III: Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC Experimental Treatment 4 Interventions

sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)

Group IV: Part B: Dose expansion Experimental Treatment 1 Intervention

sigvotatug vedotin monotherapy

Group V: Part A: Dose escalation Experimental Treatment 1 Intervention

sigvotatug 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

The newly developed 68Ga-DOTA-SETSKSF peptide effectively targets and monitors PD-L1 expression in tumors, showing high uptake in PD-L1 positive H1975 tumors compared to low uptake in PD-L1 negative A549 tumors, indicating its potential for personalized cancer treatment.

With a radiochemical purity of over 99% and stability greater than 95% in various solutions, 68Ga-DOTA-SETSKSF demonstrates a promising profile for clinical applications in imaging and monitoring tumor responses to therapies targeting the PD-1/PD-L1 pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Small Cyclic Peptide-Based 68Ga-Radiotracer for Positron Emission Tomography Imaging of PD-L1 Expression in Tumors. Liu, H., Hu, M., Deng, J., et al.[2022]

Denintuzumab mafodotin demonstrated significant anti-leukemic activity in preclinical models of pediatric acute lymphoblastic leukemia (ALL), delaying progression in seven out of eight patient-derived xenografts (PDXs) tested.

When combined with standard chemotherapy (vincristine, dexamethasone, and l-asparaginase), denintuzumab mafodotin enhanced therapeutic effects, suggesting a potential for improved treatment strategies in pediatric ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts. Jones, L., McCalmont, H., Evans, K., et al.[2023]

SGN-B7H4V is a novel antibody-drug conjugate that targets the B7-H4 immune checkpoint ligand, showing strong antitumor activity in preclinical models of breast and ovarian cancer, particularly in tumors with high B7-H4 expression.

The drug works by directly killing tumor cells through its cytotoxic payload, MMAE, and also enhances immune responses when combined with anti-PD-1 therapy, indicating its potential as an effective treatment for advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-B7H4V, an investigational vedotin ADC directed to the immune checkpoint ligand B7-H4, shows promising activity in preclinical models. Gray, E., Ulrich, M., Epp, A., et al.[2023]

The development of 68Ga-labeled adnectin protein (68Ga-BMS-986192) shows high radiochemical yields over 97% and excellent stability in human serum, making it a promising tool for imaging PD-L1 expression in tumors.

In vivo studies demonstrated that 68Ga-BMS-986192 has high uptake in PD-L1-positive tumors while showing negligible uptake in PD-L1-negative tumors, indicating its potential for accurately predicting responses to PD-1-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Preclinical Evaluation of a 68Ga-Labeled Adnectin, 68Ga-BMS-986192, as a PET Agent for Imaging PD-L1 Expression. Robu, S., Richter, A., Gosmann, D., et al.[2022]

In a prospective study involving 32 patients with neuroendocrine tumors (NETs), 68 Ga-DOTATATE PET/CT was found to detect more primary tumors compared to somatostatin receptor scintigraphy (SRS), identifying 15 out of 18 tumors versus 10 out of 18 for SRS, although the difference was not statistically significant (P = .074).

Overall, 68 Ga-DOTATATE PET/CT combined with CT and MRI detected 31 out of 33 involved regions, showing comparable efficacy to the combination of SRS, liver MRI, and thoraco-abdominopelvic CT, but it missed half of the primary lung carcinoids in patients with ectopic Cushing's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers. Gabriel, S., Garrigue, P., Dahan, L., et al.[2022]

Brentuximab vedotin is an antibody-drug conjugate that combines an anti-CD30 antibody with a powerful cytotoxic agent, showing promise in treating Hodgkin lymphoma and anaplastic large cell lymphoma.

The drug is currently under investigation in North America and Europe, highlighting its potential as a targeted therapy for specific types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

Bestatin treatment effectively suppressed tumor growth and reduced the uptake of the APN/CD13-specific radiopharmaceutical 68Ga-NODAGA-c(NGR) in both HT1080 and B16-F10 tumor models, indicating its potential as an antiangiogenic therapy.

The study demonstrated that 68Ga-NODAGA-c(NGR) can be used as a reliable radiotracer for monitoring the efficacy of therapies targeting APN/CD13, providing a method to visualize and assess treatment response in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using 68Ga-NODAGA-c(NGR) Peptide. Kis, A., Dénes, N., Szabó, JP., et al.[2022]

Radio-guided surgery (RGS) using (68)Ga-DOTATATE is feasible for identifying gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), with an 81% success rate in detecting gastric and small intestine NETs and 67% for pancreatic NETs.

The study involved 14 patients and demonstrated that RGS can accurately confirm the presence of bowel NETs and metastatic lymph nodes, suggesting it could enhance surgical outcomes, although further research is needed to assess its overall benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors. Sadowski, SM., Millo, C., Neychev, V., et al.[2021]

Brentuximab vedotin (SGN-35) is an effective antibody-drug conjugate that targets the CD30 antigen, showing response rates of 75% in Hodgkin lymphoma patients (n = 102) and 87% in anaplastic large cell lymphoma patients (n = 30) during phase II trials.

The efficacy of SGN-35 may not only stem from the direct cytotoxic effects of its drug component, MMAE, but also from its ability to signal malignant cells and affect the tumor microenvironment, potentially enhancing overall treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin (SGN-35). Katz, J., Janik, JE., Younes, A.[2019]

[68Ga]Ga-DOTA-TOC is the first FDA-approved radiopharmaceutical for imaging somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors using PET, highlighting its significance in cancer diagnostics since its approval in the U.S. in 2019.

This radiopharmaceutical effectively targets tumor cells expressing somatostatin receptors, making it useful not only for imaging but also for therapy planning and evaluating treatment responses in both localized and disseminated disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[68Ga]Ga-DOTA-TOC: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging. Hennrich, U., Benešová, M.[2020]

The study identified a series of short β/γ hybrid peptides, with BG6 showing the most potent cytotoxicity against various cancer cell lines, including breast, lung, prostate, and colon cancers, with IC50 values between 1.6 μM and 6.3 μM.

BG6 demonstrated low toxicity to normal cells and minimal hemolytic activity, while also exhibiting anti-migratory and anti-invasive properties, indicating its potential as a safe and effective cancer treatment through apoptosis induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, conformation and cytotoxic activity of short hybrid peptides containing conformationally constrained 1-(aminomethyl)cyclohexanecarboxylic acid and gabapentin. Ur Rahim, J., Ahmad, SM., Amin, T., et al.[2023]

The novel probe 68Ga-DOTA-NKL, created by combining tumor-targeting peptides, effectively targets CD13-positive tumors, showing a significant uptake in tumor cells (3.15% after 2 hours) and high tumor-to-background contrast in imaging studies.

In vivo PET imaging demonstrated that 68Ga-DOTA-NKL has promising tumor-selective properties, with uptake rates in a prostate cancer mouse model reaching 8.69% of the injected dose per gram of tissue shortly after injection, indicating its potential for diagnosing CD13-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Uniquely Modified DKL-based Peptide Probe for Positron Emission Tomography Imaging. Liu, Y., Wang, Z., Li, X., et al.[2020]

Radiolabeled DOTA-SP90 shows strong binding affinity to breast cancer cells, indicating its potential effectiveness as a targeted radiotracer for detecting tumors.

Imaging studies using nanoSPECT/CT and nanoPET/CT demonstrated that DOTA-SP90 can accumulate in both primary and metastatic breast tumors, suggesting its utility as a diagnostic agent for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging and biodistribution of radiolabeled SP90 peptide in BT-483 tumor bearing mice. Lo, WL., Liang, CH., Chen, LC., et al.[2021]

The somatostatin analogue 68Ga-DOTA NOC shows high affinity for somatostatin receptors that are overexpressed in neuroendocrine tumors, making it a promising tool for targeting these tumors.

The labeling process for 68Ga-DOTA NOC demonstrated high radiochemical purity (over 99%) and stability for at least 3 hours, indicating reliable performance across 73 labeling sessions, which is crucial for its potential clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue 68Ga DOTA NOC. Di Pierro, D., Rizzello, A., Cicoria, G., et al.[2014]

In a review of 2225 lymphoma patients from 4 randomized controlled trials, brentuximab vedotin was found to significantly increase the risk of all-grade adverse events (AEs) and high-grade AEs compared to non-brentuximab vedotin treatments.

Specific AEs associated with brentuximab vedotin included a higher risk of peripheral sensory neuropathy, pyrexia, nausea, vomiting, diarrhea, and alopecia, with particularly high risks for high-grade sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Gao, S., Zhang, M., Wu, K., et al.[2021]

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/NCT04389632

A Study of Sigvotatug Vedotin in Advanced Solid Tumors This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3010

Sigvotatug vedotin (SV), an investigational integrin beta-6 ... SV, an IB6-directed ADC, demonstrated encouraging antitumor activity and manageable safety as a monotherapy in patients (pts) with advanced NSCLC.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10690100/

SGN-B6A: A New Vedotin Antibody–Drug Conjugate ... We developed SGN-B6A as an antibody–drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) ...

5. onclive.com onclive.com/view/phase-3-evaluation-of-sigvotatug-vedotin-is-underway-in-pretreated-nonsquamous-nsclc

Phase 3 Evaluation of Sigvotatug Vedotin Is Underway in ... Phase 1 data showed a 19% overall response rate and 69% disease control rate in heavily pretreated NSCLC patients, with promising results in ...

6. 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 ... In vivo models also showed sigvotatug vedotin had antitumor activity across multiple tumor types, including NSCLC, pancreatic, pharyngeal, and ...

7. 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 ...