PF-07921585 + Sasanlimab for Cancer

No longer recruiting at 9 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: Anti-PD-(L)1 therapy

Disqualifiers: Other malignancy, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PF-07921585, alone or with sasanlimab, to determine its safety and effectiveness for people with advanced or spreading cancers. The study focuses on several cancer types, including lung, colorectal, bladder, melanoma (skin), kidney, and head and neck cancers. Participants will receive medicines through infusions or shots every three weeks, and the trial aims to observe how the cancer responds over time. The study seeks participants with specific types of these cancers who have experienced progression after standard treatments. 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 treatment.

Will I have to stop taking my current medications?

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-07921585 is designed to be safer than traditional IL-12 therapies, which often present safety issues. Early results suggest that PF-07921585 might improve treatment tolerance by targeting PD-1, a protein that helps control the immune system. This approach aims to reduce side effects common with similar treatments.

Sasanlimab, another part of the study, has been tested in other conditions, such as a type of bladder cancer. In these studies, serious side effects were rare, and most side effects were manageable. Although sasanlimab has been studied before, its combination with PF-07921585 is still under investigation for safety and effectiveness.

As the combination of PF-07921585 and sasanlimab is in the early testing phase, the main goal is to assess how well participants tolerate these treatments together. Researchers are closely monitoring for any side effects to better understand safety. Participants considering joining this trial can expect regular check-ins to address any issues promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PF-07921585 and Sasanlimab because they offer potential new ways to tackle cancer beyond the standard treatments like chemotherapy and immunotherapy. PF-07921585 is unique because it targets specific proteins involved in cancer cell growth, potentially leading to more precise and effective treatment. Meanwhile, Sasanlimab is an immune checkpoint inhibitor that helps the immune system better recognize and fight cancer cells. Together, these treatments could provide a powerful combination that enhances cancer treatment outcomes by attacking the disease from multiple angles.

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

Research has shown that PF-07921585, which targets a protein involved in the immune system, holds potential for cancer treatment. Studies on similar drugs indicate that boosting certain immune cells can help attack and shrink tumors. In this trial, participants may receive PF-07921585 alone or with sasanlimab. Previous studies suggest that sasanlimab can reduce cancer-related issues and slow cancer growth, particularly in bladder cancer. Combining PF-07921585 and sasanlimab might enhance the immune system's ability to fight cancer more effectively. Early results suggest this approach could improve outcomes for patients with advanced cancers. ^{4 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults over 18 with advanced or metastatic cancers such as lung, colorectal, bladder, skin (melanoma), kidney, and head/neck cancer. Participants must have measurable lesions and shown progression after standard treatments. Specific cohorts include those resistant to melanoma therapy, untreated lung cancer patients, and others.

Inclusion Criteria

My metastatic melanoma is resistant to certain immunotherapies and targeted therapies.

I have metastatic colorectal cancer that is not MSI-High.

I have at least one tumor that can be measured.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Monotherapy

Dose escalation of PF-07921585 as a single agent to determine the monotherapy recommended dose for further study

9 weeks

Visits every 3 weeks, with more frequent visits in the first 9 weeks

Dose Escalation Combination Therapy

Dose escalation of PF-07921585 in combination with sasanlimab to determine the recommended dose for expansion

Up to 2 years

Visits every 3 weeks

Dose Optimization/Expansion

Evaluation of PF-07921585 in combination with sasanlimab, enrolling participants into specific cohorts based on tumor type

Up to 2 years

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

28-90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• PF-07921585
• Sasanlimab

Trial Overview The trial is testing PF-07921585 alone or combined with Sasanlimab in people whose cancer has spread. Treatments are administered every three weeks via infusion or shots under the skin for up to two years if beneficial.

How Is the Trial Designed?

Group I: Part 3 Experimental Treatment 2 Interventions

Dose optimization/ expansion (combination therapy)

Group II: Part 2 Experimental Treatment 2 Interventions

Dose escalation (combination therapy)

Group III: Part 1 Experimental Treatment 1 Intervention

Dose escalation monotherapy

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

A phase I trial involving 26 patients with metastatic renal cell carcinoma (RCC) and malignant melanoma (MM) demonstrated that concurrent subcutaneous administration of IL-12 and IFN-alpha-2b is feasible, with recommended doses for further studies set at 500 ng/kg for IL-12 and 1.0 MU/m² for IFN-alpha-2b.

The treatment showed some efficacy, with partial responses in three patients and a median survival of 13.8 months, although dose-limiting toxicities such as hepatotoxicity and neutropenia were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. Alatrash, G., Hutson, TE., Molto, L., et al.[2022]

Interleukin-12 (IL-12) has shown strong antitumor, anti-metastatic, and anti-angiogenic effects in pre-clinical studies, making it a promising candidate for cancer immunotherapy.

Early phase I and II clinical trials indicate that IL-12 is less toxic compared to other immunotherapeutics like interferons or IL-2, suggesting a safer profile for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of interleukin-12 in pre-clinical and early clinical studies (Review). Golab, J., Zagozdzon, R.[2019]

Interleukin-12 (IL-12) is a promising immunomodulator for cancer treatment, showing effective destruction of cancer cells and anti-angiogenic activity, which helps inhibit tumor growth by reducing support from tumor-associated macrophages.

Inherited variations in the IL-12A and IL-12B genes can influence cancer susceptibility and may serve as potential targets for early cancer diagnosis and prevention, highlighting the importance of genetic factors in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-12: clinical usage and molecular markers of cancer susceptibility. Yuzhalin, AE., Kutikhin, AG.[2022]

IL-12 demonstrated significant antitumor activity in murine models, leading to prolonged survival and complete tumor regression, even when treatment was initiated after tumors were established.

The antitumor effects of IL-12 were linked to immune responses involving increased levels of IFN-gamma and CD8+ T cells, with minimal toxicity observed at effective doses, supporting its potential for human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. Nastala, CL., Edington, HD., McKinney, TG., et al.[2022]

In a study of 313 Korean never-smokers with advanced lung adenocarcinoma, gefitinib did not show a significant improvement in overall survival compared to gemcitabine and cisplatin chemotherapy, with median survival times of 22.3 months for gefitinib and 22.9 months for GP.

However, gefitinib demonstrated a higher 1-year progression-free survival rate (16.7%) compared to GP (2.8%), indicating it may offer some benefits in delaying disease progression despite not improving overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. Han, JY., Park, K., Kim, SW., et al.[2022]

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]

In a pilot study involving 13 patients with advanced melanoma, breast cancer, and colon cancer, the drug PD-0325901 showed significant tolerability issues, particularly at doses of 15 mg twice daily or higher, leading to early termination of the study due to adverse effects like gait disturbance and memory impairment.

Despite the safety concerns, one patient achieved a complete response and five had stable disease, suggesting that PD-0325901 may have preliminary antitumor activity, warranting further investigation at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. Boasberg, PD., Redfern, CH., Daniels, GA., et al.[2021]

In a phase 2 trial involving 126 patients with KRAS p.G12C-mutated advanced non-small-cell lung cancer (NSCLC), sotorasib demonstrated a 37.1% objective response rate, including complete responses in 3.2% of patients, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 12.5 months and a median progression-free survival of 6.8 months, with manageable safety profiles, as 69.8% of patients experienced treatment-related adverse events, mostly of grade 3 severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. Skoulidis, F., Li, BT., Dy, GK., et al.[2022]

In a phase 3 study involving 357 patients with advanced squamous non-small cell lung cancer (sqNSCLC), sintilimab combined with platinum and gemcitabine (GP) significantly improved progression-free survival (PFS) compared to GP alone, with a hazard ratio of 0.536, indicating a strong clinical benefit.

The safety profile of sintilimab-GP was acceptable, with similar rates of severe treatment-related adverse events (86.6% for sintilimab-GP vs. 83.1% for placebo-GP) and no new safety concerns identified, suggesting it is a viable first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). Zhou, C., Wu, L., Fan, Y., et al.[2022]

Immune checkpoint inhibitors are promising immunomodulatory agents that help reactivate immune cells to fight tumors, showing significant effectiveness in treating solid cancers like melanoma and non-small cell lung cancer.

Numerous clinical studies are currently investigating the benefits of these inhibitors across various cancer types, with a particular focus on their application in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. Gaynor, N., Crown, J., Collins, DM.[2022]

Citations

1. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/nct06580938

NCT06580938 | Pfizer Oncology Development Website IL-12 mutein ... Time Frame. Baseline up to 28 days after the last dose of PF-07921585 or after 90 days after the last dose of sasanlimab. Outcome ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04181788

Sasanlimab (PF-06801591, PD-1 Inhibitor) in Participants ... This study consists of 2 parts: Phase 1b part (dose escalation and dose expansion) in patients with advanced malignancies in Asia and a global Phase 2 part in ...

3. webfiles.pfizer.com webfiles.pfizer.com/file/01jqh5qsyae3923hgyst96j3sa

PD-1 Targeting Increases the Tolerance of IL-12 while ... Once tumors reached ~75mm3, mice were randomized into treatment groups and monitored for tumor size/ body weight twice weekly until tumor burden endpoint. • ...

4. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-significantly-improves-event

Pfizer's Sasanlimab Combination Significantly Improves ... Pivotal Phase 3 CREST trial results show a 32% reduction in the risk of disease-related events, including high-grade disease recurrence or ...

5. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-press-releases/159966-pfizer-s-sasanlimab-combination-significantly-improves-event-free-survival-in-bcg-naive-high-risk-non-muscle-invasive-bladder-cancer.html

Pfizer's Sasanlimab Combination Significantly Improves ... Pivotal Phase 3 CREST trial results show a 32% reduction in the risk of disease-related events, including high-grade disease recurrence or progression, ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/3414/758594/Abstract-3414-PD-1-targeting-increases-the

Abstract 3414: PD-1 targeting increases the tolerance of IL-12 ... However, fully potent IL-12 therapies have limited clinical safety profiles. We have designed PF-07921585 to overcome this challenge by ...

7. careacross.com careacross.com/clinical-trials/trial/NCT06580938

A Study to Learn About PF-07921585 Alone or With Other ... Summary: The purpose of this study is to learn about the safety and effects of the study medicine (called PF-07921585) in people with cancer that has advanced ...

8. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/pf-07921585-pfizer-metastatic-colorectal-cancer-likelihood-of-approval/

PF-07921585 by Pfizer for Metastatic Colorectal Cancer PF-07921585 is under clinical development by Pfizer and currently in Phase I for Metastatic Colorectal Cancer.

9. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/PFE-N/pressreleases/33202806/pfizers-phase-1-cancer-study-a-potential-game-changer-in-oncology/

Pfizer's Phase 1 Cancer Study: A Potential Game-Changer ... The study tests PF-07921585, an IL-12 mutein, given intravenously or subcutaneously every three weeks, and sasanlimab, an anti-PD1 antibody, ...