PF-07921585 + Sasanlimab for Cancer

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

4 Participants Needed

Trial Summary

What is the purpose of this trial?

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 or spread to other parts of the body. This study is seeking participants who have any of the following cancer types: * non-small cell lung cancer * colorectal cancer * bladder cancer * melanoma (a type of skin cancer) * kidney cancer * head and neck cancer Participants will receive the study medicine PF-07921585 alone or in combination with another study medicine called sasanlimab at the study clinic. PF-07921585 will be given as an infusion into a vein or as shots under the skin, once every 3 weeks. Sasanlimab will be given as shots under the skin, also once every 3 weeks. The experiences of participants receiving the study medicine will be studied to help see if the study medicine is safe and effective. Participants may receive study medicine for up to 2 years, depending on how the cancer responds to the study treatment. Participants may continue receiving study medicine after 2 years if there are any benefits from the study treatment. Participants will attend visits once every 3 weeks with the first 9 weeks having more frequent visits, to check the safety of the study 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.

What data supports the effectiveness of the drug PF-07921585 + Sasanlimab for cancer?

Research shows that IL-12, a component of the treatment, has been effective in reducing tumors and prolonging survival in animal studies, and has shown promise in early human trials for various cancers. Additionally, immune checkpoint inhibitors, similar to Sasanlimab, have demonstrated impressive results in treating several types of solid cancers. ^{1 2 3 4 5}

What makes the drug PF-07921585 + Sasanlimab unique for cancer treatment?

The combination of PF-07921585 and Sasanlimab is unique because it involves an IL-12 mutein, which is a modified version of a protein that can stimulate the immune system to fight cancer, potentially offering a novel approach compared to traditional chemotherapy or other existing cancer treatments. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. [2022]

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

Interleukin-12: clinical usage and molecular markers of cancer susceptibility. [2022]

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

Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Antitumor effects of interleukin-12 in pre-clinical and early clinical studies (Review). [2019]

5. United States 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. [2022]

6. United States 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. [2022]

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. [2021]

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

Sotorasib for Lung Cancers with KRAS p.G12C Mutation. [2022]

10. United States 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). [2022]