SGN-B6A for Cancer

Recruiting in Palo Alto (17 mi)

+49 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Seagen Inc.

Must not be taking: Corticosteroids, MMAE agents

Disqualifiers: CNS metastases, Neuropathy, ILD, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called sigvotatug vedotin alone and with other treatments to see if it is safe and effective for people with solid tumors. It will also check for any side effects. The study includes different parts to determine the best dose and to see how well the drug works alone and in combination with other treatments.

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.

What data supports the effectiveness of the drug SGN-B6A for cancer treatment?

The research highlights the effectiveness of targeting PD-L1, a protein that helps tumors evade the immune system, using imaging agents like 68Ga-labeled compounds. This suggests that therapies targeting PD-L1, such as those involving Pembrolizumab (a component of the SGN-B6A treatment), may be effective in treating cancers by enhancing the immune system's ability to attack tumor cells. ^{1 2 3 4 5}

What safety data exists for SGN-B6A and related treatments?

Brentuximab vedotin, which uses a similar vedotin linker-payload system as SGN-B6A, has been shown to increase the risk of certain side effects in lymphoma patients, including nerve damage, fever, nausea, vomiting, diarrhea, and hair loss. ^{6 7 8 9 10}

What makes the drug SGN-B6A unique for treating cancer?

SGN-B6A (Sigvotatug Vedotin) is unique because it targets specific receptors on cancer cells, potentially offering a more targeted approach compared to traditional chemotherapy, which affects both healthy and cancerous cells. ^{11 12 13 14 15}

Research Team

Medical Monitor

Principal Investigator

Seagen Inc.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Pembrolizumab (Monoclonal Antibodies)
• SGN-B6A (Monoclonal Antibodies)

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.

Participant Groups

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 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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A Novel Small Cyclic Peptide-Based 68Ga-Radiotracer for Positron Emission Tomography Imaging of PD-L1 Expression in Tumors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[68Ga]Ga-DOTA-TOC: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin (SGN-35). [2019]

10. England 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. [2023]

11. United States 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. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Synthesis, conformation and cytotoxic activity of short hybrid peptides containing conformationally constrained 1-(aminomethyl)cyclohexanecarboxylic acid and gabapentin. [2023]

13. United Arab Emirates pubmed.ncbi.nlm.nih.gov

A Uniquely Modified DKL-based Peptide Probe for Positron Emission Tomography Imaging. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Imaging and biodistribution of radiolabeled SP90 peptide in BT-483 tumor bearing mice. [2021]

15. England pubmed.ncbi.nlm.nih.gov

Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue 68Ga DOTA NOC. [2014]