PF-08046032 + Sasanlimab for Cancer

Recruiting at 2 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

220 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug PF-08046032 + Sasanlimab for cancer?

Sasanlimab, a drug that blocks a protein called PD-1, has shown promise in treating various cancers by helping the immune system attack cancer cells. It has been effective in non-small-cell lung cancer and urothelial carcinoma, and similar drugs have been successful in treating other advanced cancers. ^{1 2 3 4 5}

What safety data exists for Sasanlimab in humans?

Sasanlimab, a type of drug that helps the immune system fight cancer, has been studied for its safety in humans. While specific safety data for Sasanlimab alone is not detailed in the provided research, similar drugs targeting the same pathway have shown manageable safety profiles, with common side effects including skin issues like rash and fatigue. ^{1 6 7 8 9}

What makes the drug PF-08046032 + Sasanlimab unique for cancer treatment?

This treatment combines PF-08046032 with Sasanlimab, a monoclonal antibody that targets the PD-1 receptor, which is involved in preventing the immune system from attacking cancer cells. Sasanlimab is administered subcutaneously (under the skin), which may offer a more convenient option compared to intravenous (into the vein) treatments. ^{1 2 3 10 11}

What is the purpose of this trial?

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 called sasanlimab, for the treatment of advanced cancers. The effects are studied in adult participants with certain types of lymphomas or solid tumors that are advanced or metastatic (spread to other parts of the body). The study has three parts: * Part A will test PF-08046032 alone at increasing dose levels in participants with certain lymphomas (cancer that begins in cells of the immune system) and in participants with certain solid tumors whose disease has worsened on or after standard treatments. * Part B will test PF-08046032 (at selected doses) and sasanlimab in participants with certain solid tumors, including those whose disease has worsened on or after standard treatments as well as participants before receiving standard treatments. * Part C will further test the combination of PF-08046032 and sasanlimab in participants with specific types of solid tumors based on the results from Part A and Part B of the study. All participants will receive the study drug PF-08046032. Only participants in Part B and Part C of the study will also receive sasanlimab. PF-08046032 will be given as an intravenous (IV) infusion, which means it will be injected directly into a vein. Sasanlimab will be given as a subcutaneous injection, which means it will be injected under the skin.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

1. France 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. [2022]

2. England 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. [2023]

3. United States 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. [2021]

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

Dostarlimab: From preclinical investigation to drug approval and future directions. [2023]

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

Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody. [2021]

6. England 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. [2023]

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

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

8. Spain 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. [2021]

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

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

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

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. [2019]

11. United States 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. [2023]