PF-07826390 for Cancer

Recruiting at 12 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Organ dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

5 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the: * safety (the effect of the study medicine on the participant's body), * effects of the study medicine alone or in combination with sasanlimab - * the best amount of the study medicine. This study is seeking participants who have solid tumors (An abnormal mass of tissue) that: * have advanced (cancer that does not disappear or stay away with treatment) or * are metastatic (has spread to other parts of the body). This includes (but limited to) the following cancer types: * Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body. * Colorectal Cancer (CRC): This is a disease where cells in the colon or rectum grow out of control. * Renal Cell Carcinoma (RCC): This is a cancer that starts in the kidney. All participants in this study will receive the study medication (PF-07826390) as an IV infusion (given directly into a vein) at the study once every four weeks in 28 day cycles. The study participants depending on the group enrolled in, will receive the study medication (PF-07826390 alone or in combination with other anti-cancer medications (sasanlimab). Sasanlimab is given as a shot under the skin every 4 weeks. Participants can continue to take the study medication (PF-07826390) until their cancer is no longer responding. Participants who are taking sasanlimab may receive it for up to 2 years. The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective. Participants will be involved in this study for up to 4 years. During this time, participants will have a study visit every week. The participants after stopping the study medicine (at about 2 years) will be followed for another two years to see how the participants are doing.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anticancer therapy at least 4 weeks before starting the study medication. However, the protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug sasanlimab for cancer treatment?

Research shows that sasanlimab, which targets the PD-1 receptor, has improved outcomes in patients with non-small-cell lung cancer and urothelial carcinoma. Anti-PD-1 drugs like sasanlimab have been effective in improving patient survival in various cancers. ^{1 2 3 4 5}

What makes the drug PF-07826390 unique for cancer treatment?

PF-07826390, also known as sasanlimab, is unique because it is an immune checkpoint inhibitor that targets PD-1, potentially enhancing the immune system's ability to fight cancer cells. This mechanism is similar to other drugs like pembrolizumab and pucotenlimab, but each drug may have different efficacy and safety profiles in various cancer types. ^{6 7 8 9 10}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors, including specific types of lung, colorectal, and kidney cancers. Participants must have tried certain standard treatments without success or be unable to tolerate them. They should have at least one measurable tumor lesion and be able to provide tissue samples.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and has either spread or not responded to treatment.

My cancer has worsened despite previous anti-PD-(L)1 therapy.

I have NSCLC and have been treated with platinum-based chemo and anti-PD-(L)1 or cannot tolerate standard treatments.

Exclusion Criteria

My kidney, liver, and bone marrow are not working well.

I had a severe reaction to previous immune therapy that needed treatment.

I haven't had cancer treatment in the last 4 weeks or 5 half-lives, whichever is shorter.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-07826390 as an IV infusion every four weeks in 28-day cycles, alone or in combination with sasanlimab

Up to 2 years

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after stopping the study medication

2 years

Regular follow-up visits

Extension

Participants may continue to receive PF-07826390 until their cancer is no longer responding

Up to 4 years total participation

Treatment Details

Interventions

• PF-07826390
• sasanlimab
• SOC

Trial Overview The study tests PF-07826390 alone or combined with sasanlimab (an anti-cancer medication) in people with cancer. It aims to determine the safest and most effective dosage. Patients will receive these medications through IV infusion or shots under the skin every four weeks.

Participant Groups

Group I: Part 2C: PF-07826390 + SOC Experimental Treatment 2 Interventions

PF-07826390 + SOC (anti-PD-1 + platinum -based chemo) dose expansion for a PDx-naive NSCLC 1L at prescribed dose and frequency in 28-day cycles

Group II: Part 2B: PF-07826390 Experimental Treatment 1 Intervention

PF-07826390 dose expansion in NSCLC 2L+ at prescribed dose and frequency in 28-day cycles

Group III: Part 2A (Arm 3): PF-07826390 + sasanlimab Experimental Treatment 2 Interventions

PF-07826390 + sasanlimab dose expansion in RCC 2L+ at prescribed dose and frequency in 28-day cycles

Group IV: Part 2A (Arm 2): PF-07826390 + sasanlimab Experimental Treatment 2 Interventions

PF-07826390 + sasanlimab dose expansion in MSS CRC 2L+ at prescribed dose and frequency in 28-day cycles

Group V: Part 2A (Arm 1): PF-07826390 + sasanlimab Experimental Treatment 2 Interventions

PF-07826390 + sasanlimab dose expansion in NSCLC 2L+ at prescribed dose and frequency in 28-day cycles

Group VI: Part 1B: PF-07826390 + sasanlimab Experimental Treatment 2 Interventions

PF-07826390 + sasanlimab at prescribed dose and frequency in 28-day cycles

Group VII: Part 1A: PF-07826390 Monotherapy Experimental Treatment 1 Intervention

PF-07826390 monotherapy at prescribed dose and frequency in 28-day cycles

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 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]

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 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 meta-analysis of 27 randomized controlled trials involving 15,590 patients with advanced non-small cell lung cancer, treatment effect sizes for progression-free survival (PFS) and overall survival (OS) were found to be comparable, suggesting that PFS can be a reliable endpoint in clinical trials.

However, the analysis indicated that PFS may not be as reliable for trials using immunotherapy as a second-line treatment, highlighting the need for caution when interpreting PFS data without OS outcomes in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis. Zhou, Z., Ren, S., Chen, L., et al.[2022]

Anlotinib significantly improved overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) regardless of their EGFR mutation status, with OS of 10.7 months for EGFR-positive patients and 8.9 months for EGFR-negative patients compared to placebo.

The efficacy of anlotinib was demonstrated through substantial improvements in PFS as well, with 5.6 months for EGFR-positive and 5.4 months for EGFR-negative patients, indicating that anlotinib is a viable third-line treatment option for NSCLC patients irrespective of their genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study. Zhao, Y., Wang, Q., Zhang, L., et al.[2022]

In a phase 2 trial involving 33 patients with advanced sarcomas, the combination of axitinib and pembrolizumab showed a promising 3-month progression-free survival rate of 65.6%, with even higher rates of 72.7% for patients with alveolar soft-part sarcoma (ASPS).

The treatment was associated with manageable side effects, with 21% of patients experiencing serious adverse events, but no treatment-related deaths, indicating a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Wilky, BA., Trucco, MM., Subhawong, TK., et al.[2020]

Pucotenlimab is a monoclonal antibody that targets PD-1, effectively blocking its interaction with PD-L1 and PD-L2, which helps restore immune cell function against various solid tumors.

In July 2022, pucotenlimab received conditional approval in China for treating advanced solid tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) characteristics, particularly after previous therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pucotenlimab: First Approval. Dhillon, S.[2022]

Axitinib is an oral medication that inhibits key receptors involved in tumor growth and has shown activity against various solid tumors, including thyroid, pancreatic, lung, and breast cancers, based on Phase II trials.

While common side effects include fatigue and hypertension, axitinib was generally well tolerated, and larger randomized studies were underway to further evaluate its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Choueiri, TK.[2018]

In a multicenter phase II study involving 53 Japanese patients with advanced colorectal cancer, the FOLFOX4 regimen (oxaliplatin, levoforinate, and infusional 5-fluorouracil) demonstrated a partial response rate of 20.8%, indicating its efficacy as a second-line therapy.

The treatment showed good tolerability, with manageable toxicity, primarily neutropenia occurring in 43.1% of patients, suggesting that FOLFOX4 is a promising option for patients who have not responded to first-line chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: a Japanese experience. Ogata, Y., Tokunaga, S., Emi, Y., et al.[2021]

In a phase II trial involving 25 patients with RAS-mutant, microsatellite stable metastatic colorectal cancer, the combination of sintilimab, bevacizumab, oxaliplatin, and capecitabine showed a high objective response rate of 84% and a disease control rate of 100%, indicating promising anti-tumor activity.

The treatment was generally well-tolerated, with manageable adverse events; the most common were anemia and neutropenia, but no grade 5 adverse events occurred, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial. Fang, X., Zhu, N., Zhong, C., et al.[2023]

References

1. 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]

2. 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]

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. China pubmed.ncbi.nlm.nih.gov

Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis. [2022]

5. China pubmed.ncbi.nlm.nih.gov

The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. [2020]

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

Pucotenlimab: First Approval. [2022]

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

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: a Japanese experience. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial. [2023]