PF-08046032 + Sasanlimab for Cancer

Not currently recruiting at 8 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Disqualifiers: Peripheral neuropathy, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new medicine, PF-08046032, is safe and effective for people with advanced cancers, either alone or combined with sasanlimab (an immunotherapy). The focus is on patients whose cancer has spread and who have not responded well to standard treatments. Participants will receive the treatment as an infusion or injection. This trial may suit those with certain lymphomas or solid tumors that have worsened despite previous treatments. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for 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 PF-08046032 is a new treatment under study for cancer. It targets specific immune cells in tumors. Early results suggest it might be safe, as it aims to remove specific cells without harming other important ones. However, its safety for humans remains unconfirmed.

When combined with sasanlimab, a drug that boosts the immune system, researchers are still collecting safety data. Sasanlimab has been studied before and showed promise in slowing cancer when used with other treatments. However, like PF-08046032, its safety in this specific combination is still under review.

Since this trial is in an early stage, it primarily aims to determine the safety of these treatments for humans. Participants should be aware that, due to the trial's early stage, safety information is still being gathered and studied. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PF-08046032 and Sasanlimab for cancer treatment because they offer unique ways to tackle the disease. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, PF-08046032 is administered intravenously and may target specific pathways involved in cancer cell growth, potentially leading to fewer side effects. Sasanlimab, given as a subcutaneous injection, is an immunotherapy that could boost the body's own immune system to fight cancer more effectively. Together, these drugs might provide a more targeted and personalized approach to cancer treatment, which is why there's a buzz around them in the medical community.

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

Research has shown that PF-08046032, one of the treatments in this trial, shows promise in fighting certain types of cancer when used alone. It targets specific immune cells in tumors that aid their growth, potentially shrinking tumors more effectively.

In this trial, some participants will receive PF-08046032 combined with sasanlimab. Studies suggest that this combination yields even better results. Sasanlimab has improved outcomes in certain cancer cases. Together, these treatments could offer a new approach to treating advanced or hard-to-treat cancers. ^{1 2 3 4 5}

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 or metastatic lymphomas and solid tumors, including squamous cell carcinoma and melanoma. Participants must have progressed after standard treatments or not received certain therapies yet. They need to provide tumor tissue samples, have a good performance status (able to carry out daily activities), and measurable disease according to specific criteria.

Inclusion Criteria

Histological or cytological diagnosis of metastatic or unresectable malignancy: Participants with lymphomas (cHL, PTCL, large B-cell lymphoma) who have progressed on/after standard therapies, Participants with solid tumors (NSCLC, HNSCC, melanoma, or other limited tumor types) who have progressed on or following prior immune checkpoint inhibitor if indicated and available, Participants with solid tumors who have either progressed on/after prior immune checkpoint inhibitor, or who have not received prior immune checkpoint inhibitor therapy, Participants with selected tumor type who have not received systemic anticancer treatment for the tumor type (including prior immune checkpoint inhibitor), Measurable disease as defined by Lugano Classification for lymphomas or RECIST 1.1 for solid tumors, Able to provide tumor tissue(s) as defined by the protocol depending on the Part of the study at enrollment, ECOG Performance Status score 0 or 1

Exclusion Criteria

Ongoing peripheral neuropathy, History of significant immune-mediated adverse event considered related to prior immune-modulatory therapy, Known or suspected active autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

PF-08046032 is administered alone at increasing dose levels to participants with certain lymphomas and solid tumors.

4 weeks

Weekly visits for dose escalation

Treatment Part B

PF-08046032 and sasanlimab are administered to participants with certain solid tumors.

4 weeks

Weekly visits for combination therapy

Treatment Part C

Further testing of PF-08046032 and sasanlimab combination in specific solid tumors based on results from Part A and Part B.

4 weeks

Weekly visits for combination therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PF-08046032
• Sasanlimab

Trial Overview

PF-08046032 alone and in combination with sasanlimab are being tested across three parts of the study: increasing doses in Part A, selected doses alongside sasanlimab in Part B, and further testing based on earlier results in Part C. PF-08046032 is given via IV infusion; sasanlimab by subcutaneous injection.

How Is the Trial Designed?

Group I: PF-08046032 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

PF-08046032 will be given as an intravenous (IV) infusion.

Group II: PF-08046032 + Sasanlimab Combination Safety Evaluation Experimental Treatment 2 Interventions

PF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.

Group III: PF-08046032 + Sasanlimab Combination Expansion Cohort Experimental Treatment 2 Interventions

PF-08046032 will be given as an intravenous (IV) infusion and sasanlimab will be administered as a subcutaneous injection.

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

Sasanlimab, an antibody targeting the PD-1 receptor, was well tolerated in patients with non-small-cell lung cancer (NSCLC) and urothelial carcinoma, with only 13.2% experiencing severe treatment-related side effects.

The treatment showed promising efficacy, with objective response rates of 16.4% in NSCLC and 18.4% in urothelial carcinoma, particularly in patients with high PD-L1 expression and tumor mutational burden, suggesting it may be a viable option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma. Cho, BC., Penkov, K., Bondarenko, I., et al.[2023]

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Sasanlimab, an anti-PD-1 monoclonal antibody, shows efficacy in treating advanced solid tumors, with response significantly associated with baseline tumor mutational burden (TMB), PD-L1, and CD8 expression in a study involving 38 patients.

The study highlights that higher expression levels of genes related to interferon-γ and PD-1 signaling pathways correlate with better responses to sasanlimab, indicating its immunomodulatory mechanism across various tumor types and administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration. Hu-Lieskovan, S., Braiteh, F., Grilley-Olson, JE., et al.[2022]

In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.

Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]

In a study of 397 patients with nonsquamous non-small cell lung cancer (NSCLC), the combination of sintilimab and chemotherapy significantly improved overall survival (OS) compared to chemotherapy alone, with a median OS not reached versus 16.8 months for the placebo group.

High expression of the MHC class II antigen presentation pathway was strongly associated with better progression-free survival (PFS) and OS, indicating that this biomarker could help identify patients who would benefit most from the sintilimab and chemotherapy combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study. Yang, Y., Sun, J., Wang, Z., et al.[2021]

Cadonilimab, a bispecific PD-1/CTLA-4 antibody, demonstrated a manageable safety profile with 28% of patients experiencing grade 3-4 treatment-related adverse events, indicating it can be safely administered to patients with advanced solid tumors.

In a phase 2 trial, cadonilimab showed promising antitumor activity, with an objective response rate of 32.3% in cervical cancer patients, suggesting its potential effectiveness in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Gao, X., Xu, N., Li, Z., et al.[2023]

In a four-year study of 80 patients with non-small cell lung cancer treated with anti-PD-1 and anti-PD-L1 therapies, significant overall survival rates were observed, particularly with nivolumab and pembrolizumab, showing 79.7% survival at 6 months and 100% at first-line treatment for pembrolizumab.

Adverse events were common, occurring in over 84% of patients, with fatigue and respiratory issues being the most reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. Zayas-Soriano, M., Bonete-Sánchez, M., Campillo-López, J., et al.[2021]

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]

Citations

1.

aacrjournals.org

aacrjournals.org/mct/article/24/7/963/763162/PF-08046032-A-Novel-Investigational-CD25-Directed

PF-08046032: A Novel, Investigational CD25-Directed ...

In a human CD25 transgenic mouse model bearing MC38 tumors, PF-08046032 showed antitumor activity and effective targeting of intratumoral Tregs. Combining a ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06870487

NCT06870487 | A Study to Learn About the ...

The purpose of this study is to learn about the effects of a new study medicine called PF-08046032, when taken alone and when taken with another medicine ...

3.

jitc.bmj.com

jitc.bmj.com/content/12/Suppl_2/A1165

1045 PF-08046032: a novel, investigational CD25-directed ...

Conclusions PF-08046032 represents an innovative therapeutic approach for the depletion of intratumoral Tregs that may offer an improved safety ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40293942/

PF-08046032: A Novel, Investigational CD25-Directed ...

PF-08046032 showed dose-dependent antitumor activity in CD25-expressing human lymphoma xenograft models, whereas a similarly detuned anti-mouse ...

5.

pfizeroncologydevelopment.com

pfizeroncologydevelopment.com/clinical_trial/NCT06870487

Clinical Trial Details | Pfizer Oncology Development Website

An Open-Label Phase 1 Study to Evaluate PF-08046032 as Monotherapy and Part of Combination Therapy in Participants With Advanced Malignancies. Phase 1.