SGN-PDL1V for Cancer

Recruiting at 55 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Seagen Inc.

Must not be taking: Anti-PD-L1, MMAE

Disqualifiers: Recent malignancy, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, SGN-PDL1V, alone and with pembrolizumab, in patients with advanced solid tumors. The goal is to see if these treatments are safe and effective. SGN-PDL1V targets cancer cells directly, while pembrolizumab helps the immune system fight the cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken an anti-PD-L1 agent recently. It's best to discuss your current medications with the study team to see if they might affect your eligibility.

What data supports the effectiveness of the drug SGN-PDL1V for cancer?

Research shows that drugs targeting PD-L1, like SGN-PDL1V, have been effective in improving survival in lung cancer patients by helping the immune system better recognize and attack cancer cells. Additionally, high levels of PD-L1 expression in tumors have been linked to better responses to these types of treatments. ^{1 2 3 4 5}

What safety information is available for SGN-PDL1V (also known as PF-08046054) in humans?

While specific safety data for SGN-PDL1V in humans is not available, similar PD-L1 inhibitors have been shown to be generally safe, though they can cause side effects like lung inflammation, liver inflammation, and inflammation of the colon. It's important to discuss potential risks with your healthcare provider. ^{6 7 8 9 10}

What makes the drug SGN-PDL1V unique for cancer treatment?

SGN-PDL1V is unique because it targets the PD-L1 protein, which helps cancer cells evade the immune system, potentially enhancing the body's ability to fight cancer. This approach is different from traditional chemotherapy, which directly targets and kills cancer cells. ^{1 4 7 11 12}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with certain advanced solid tumors like lung, breast, esophageal cancer or melanoma that have spread and can't be surgically removed. Participants must have tried standard treatments without success or cannot tolerate them. They should be relatively active and well (ECOG score of 0 or 1) and not have had specific recent cancers, brain metastases, severe neuropathy, or treatment with similar drugs.

Inclusion Criteria

Parts A and B: Participants must have one of the following histologically- or cytologically-confirmed metastatic or unresectable solid tumor types: Non-small cell lung cancer (NSCLC), Head and neck squamous cell carcinoma (HNSCC), Esophageal squamous cell carcinoma (SCC), Triple negative breast cancer (TNBC). Participants must have disease that is relapsed or refractory, that has progressed on approved therapies, be intolerant to or refused such therapies, or such and therapies are contraindicated and in the judgement of the investigator, should have no appropriate SoC therapeutic option. Participants must have PD-L1 expression based on historical testing. Parts C: Participants must have disease that is relapsed or refractory or be intolerant to SoC therapies and must have one of the following tumor types: HNSCC, NSCLC, Esophageal SCC, Ovarian cancer, Melanoma, TNBC, Gastric cancer. Participants must have been previously tested for PD-L1 expression and should have PD-L1 expression ≥1 or <1 by CPS or TPS based on historical testing. Parts D: Participants must have histologically or cytologically-confirmed disease of the HNSCC. Participants must have PD-L1 expression based on historical testing. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Measurable disease per RECIST v1.1 at baseline.

Exclusion Criteria

History of another malignancy within 3 years of first dose of study treatment or any evidence of residual disease from a previously diagnosed malignancy. Known active central nervous system metastases. Participants with previously-treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment, have no new or enlarging brain metastases, and are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study treatment. Lepto-meningeal disease. Prior treatment with an anti-PD-L1 agent within less than 5 half-lives. Previous receipt of a monomethylauristatin E (MMAE)-containing agent. Pre-existing neuropathy ≥Grade 2 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Parts A and B)

Determine the appropriate dose of PF-08046054/SGN-PDL1V for participants

8-12 weeks

Safety and Efficacy Evaluation (Part C)

Evaluate the safety and efficacy of PF-08046054/SGN-PDL1V at the determined dose

12-24 weeks

Combination Therapy Evaluation (Parts D and E)

Assess the safety and efficacy of PF-08046054/SGN-PDL1V with pembrolizumab

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• SGN-PDL1V (PD-L1 Inhibitor)

Trial Overview SGN-PDL1V is being tested to determine its safety and effectiveness in treating various types of advanced solid tumors. The study has three parts: Parts A and B will decide the right dose; Part C will test this dose further for safety outcomes and how well it works against the cancer.

Participant Groups

Group I: PF-08046054 Monotherapy Experimental Treatment 1 Intervention

PF-08046054 monotherapy

Group II: PF-08046054 Combination Therapy Experimental Treatment 2 Interventions

PF-08046054 + pembrolizumab

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

In a study of 158 advanced biliary tract cancer patients, higher levels of soluble PD-L1 (sPDL1) in serum were associated with significantly worse overall survival, indicating its potential as a prognostic biomarker.

Patients with sPDL1 levels of 0.94 ng/mL or higher had a median overall survival of 7.93 months compared to 14.10 months for those with lower levels, highlighting sPDL1 as an independent poor prognostic factor alongside the neutrophil-to-lymphocyte ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy. Ha, H., Nam, AR., Bang, JH., et al.[2022]

This study measured PDL1 expression in 38 osteosarcoma tumor samples and found that high levels of PDL1 are present in a subset of these tumors, indicating a potential target for immunotherapy.

The research also revealed a positive correlation between high PDL1 expression and the presence of tumor-infiltrating lymphocytes (TILs), suggesting that PDL1 may play a role in the immune response within osteosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed cell death ligand 1 expression in osteosarcoma. Shen, JK., Cote, GM., Choy, E., et al.[2022]

Immunotherapy, particularly checkpoint blockade targeting PD1, has shown superior survival rates and durable responses in metastatic non-small-cell lung cancer compared to traditional chemotherapy, especially in patients with high PDL1 expression.

These immunotherapeutic agents generally have tolerable safety profiles, although rare cases of pneumonitis can occur, and PDL1 expression serves as a predictive biomarker for treatment response, highlighting the importance of minimally invasive testing methods for tumor samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Era of Checkpoint Blockade in Lung Cancer: Taking the Brakes Off the Immune System. Moon, EK., Langer, CJ., Albelda, SM.[2019]

In a retrospective study of 11 patients with previously treated non-small cell lung cancer (NSCLC), nivolumab showed a median progression-free survival (PFS) of 8 months and a median overall survival (OS) of 15 months, indicating its efficacy as a second-line treatment option.

The treatment was generally well tolerated, with most side effects being mild (grade 1 and 2), although two patients experienced more severe (grade 3/4) pneumonitis, highlighting the importance of monitoring for potential serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The real-world experience with nivolumab in previously treated patients with advanced non-small cell lung cancer from a cancer center in India. Abbas, W., Acharya, RP., Pandit, A., et al.[2022]

In a meta-analysis of 12 studies involving 1188 lung cancer patients, high levels of soluble PD-L1 (sPD-L1) were linked to significantly worse overall survival (OS) and progression-free survival (PFS) in patients receiving immune checkpoint inhibitors, indicating its potential as a negative prognostic factor.

Additionally, high sPD-L1 levels were associated with poorer OS and lower objective response rates in patients treated with non-immune checkpoint inhibitor therapies, suggesting that sPD-L1 could serve as a predictive biomarker for treatment outcomes in lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble PD-L1 as a predictive biomarker in lung cancer: a systematic review and meta-analysis. Cheng, Y., Wang, C., Wang, Y., et al.[2022]

PD-1/PD-L1 inhibitors are effective as front-line treatments for various cancers, but their use is limited by serious immune-related side effects, highlighting the need for safer alternatives.

The review discusses the mechanisms of action of these inhibitors and presents clinical trial data, emphasizing the importance of monitoring adverse reactions to improve treatment strategies and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy. Ai, L., Chen, J., Yan, H., et al.[2021]

The study successfully developed a blocking anti-PDL1 single-domain antibody (sdAb) that, when vectorized into a vaccinia virus, showed superior PDL1 blocking activity compared to a full-length antibody, enhancing the potential for anti-tumor immune responses.

The research also identified an optimal tumor necrosis factor superfamily (TNFSF) fusion construct that significantly reduced tumor cell activity, emphasizing the importance of early selection of recombinant viruses in developing effective immunomodulatory therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and selection of anti-PD-L1 single-domain antibody and tumor necrosis factor superfamily ligands for an optimal vectorization in an oncolytic virus. Remy, C., Pintado, E., Dunlop, M., et al.[2023]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

The novel PD-L1 B-cell peptide vaccine (PDL1-Vaxx) has shown strong immunogenicity and the ability to inhibit tumor growth in various animal models, demonstrating its potential as a safe checkpoint inhibitor vaccine.

When combined with the HER-2 vaccine (B-Vaxx), PDL1-Vaxx exhibited synergistic effects in tumor inhibition, suggesting that combining immuno-oncology agents could enhance treatment efficacy for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A newly discovered PD-L1 B-cell epitope peptide vaccine (PDL1-Vaxx) exhibits potent immune responses and effective anti-tumor immunity in multiple syngeneic mice models and (synergizes) in combination with a dual HER-2 B-cell vaccine (B-Vaxx). Guo, L., Overholser, J., Darby, H., et al.[2022]

PD-L1 checkpoint inhibitors, like durvalumab, have shown significant efficacy in treating various solid tumors, including lung cancer and breast cancer, by suppressing tumor growth and improving patient survival.

While PD-L1 therapy is generally safe, it can cause adverse reactions such as pneumonitis and colitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. Chen, M., Jiang, J., Chen, J., et al.[2023]

PDL1 is a key protein that helps tumors evade the immune system by binding to PD1 on T cells, which can inhibit T cell responses and promote cancer growth.

Researchers developed three specific nanobodies targeting PDL1 using phage display technology from a dromedary camel immune library, highlighting a novel approach to potentially enhance cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanobody against PDL1. Li, S., Jiang, K., Wang, T., et al.[2020]

In a study of 330 lung cancer patients, those with adenocarcinoma showed the highest rates of EGFR and KRAS gene mutations, indicating these mutations are particularly common in this type of lung cancer.

PD-L1 expression was significantly higher in non-small cell lung cancer (NSCLC) patients compared to other lung cancer types, suggesting a potential target for immunotherapy in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation on the Distribution of EGFR, KRAS and BRAF Genes and the Expression of PD-L1 in Different Types of Lung Cancer. Zhao, R., Gao, S., He, H., et al.[2022]

References

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

Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy. [2022]

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

Programmed cell death ligand 1 expression in osteosarcoma. [2022]

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

The Era of Checkpoint Blockade in Lung Cancer: Taking the Brakes Off the Immune System. [2019]

4. India pubmed.ncbi.nlm.nih.gov

The real-world experience with nivolumab in previously treated patients with advanced non-small cell lung cancer from a cancer center in India. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Soluble PD-L1 as a predictive biomarker in lung cancer: a systematic review and meta-analysis. [2022]

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

Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Design and selection of anti-PD-L1 single-domain antibody and tumor necrosis factor superfamily ligands for an optimal vectorization in an oncolytic virus. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

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

A newly discovered PD-L1 B-cell epitope peptide vaccine (PDL1-Vaxx) exhibits potent immune responses and effective anti-tumor immunity in multiple syngeneic mice models and (synergizes) in combination with a dual HER-2 B-cell vaccine (B-Vaxx). [2022]

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

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Nanobody against PDL1. [2020]

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

Evaluation on the Distribution of EGFR, KRAS and BRAF Genes and the Expression of PD-L1 in Different Types of Lung Cancer. [2022]