PF-07934040 + Other Anti-Cancer Therapies for Non-Small Cell Lung Cancer

Recruiting at 30 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pneumonitis, Autoimmune disease, GI disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, PF-07934040 (also known as PF-4040), for individuals with advanced solid tumors that have a KRAS gene mutation. The goal is to determine the drug's safety and optimal dosage, both alone and in combination with other cancer treatments. The trial seeks participants with specific cancers, such as non-small cell lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma, who have not responded to standard treatments. Participants will take the study medication in cycles and may also receive additional treatments through IV. The trial aims to assess the safety and effectiveness of this approach in treating these cancers. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to understand how your current medications might interact with the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that PF-07934040 is under study to assess its safety both alone and in combination with other cancer treatments. Although detailed safety information for PF-07934040 is not widely available yet, the study aims to determine the optimal dose and identify possible side effects.

Pembrolizumab is one of the main drugs used with PF-07934040 in these combination treatments. Studies have found that Pembrolizumab is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). Patients have reported that Pembrolizumab, whether used alone or with chemotherapy, provides lasting benefits and has manageable side effects.

As a Phase 1 study, the primary focus is on testing safety and identifying any side effects. This phase typically involves small groups of people, allowing researchers to closely monitor how the treatment is tolerated. Participants in this trial will be observed carefully to understand how their bodies react to the treatment, enabling early detection of any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PF-07934040 for non-small cell lung cancer (NSCLC) because it offers a novel approach compared to existing treatments. Most current NSCLC therapies rely on targeting specific genetic mutations or proteins, like EGFR or ALK inhibitors, and traditional chemotherapy. PF-07934040, however, is being explored both as a monotherapy and in combination with other anti-cancer agents, which could enhance its effectiveness. It stands out due to its versatility in combination with Pembrolizumab and chemotherapy, potentially improving outcomes for patients with various tumor profiles. Additionally, its use in combination therapies aims to tackle the cancer from multiple angles, potentially increasing efficacy and reducing resistance.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Studies have shown that PF-07934040 targets a specific gene mutation called KRAS, which often causes uncontrolled cell growth in cancers such as non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer. Research suggests that targeting this mutation can help slow cancer growth. In this trial, some participants will receive PF-07934040 as a monotherapy, while others will receive it with other cancer drugs. Early results indicate that PF-07934040 might be effective both alone and in combination with other cancer drugs. Studies also show that PF-07934040 has promising potential, especially when combined with treatments like pembrolizumab, to improve outcomes for patients with advanced cancers. ^{1 2 6 7 8}

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 solid tumors that have a KRAS gene mutation and have progressed after standard treatments. It includes specific cancers like NSCLC, CRC, and PDAC. Participants must have tried previous therapies without success and should be in good physical condition (ECOG PS 0 or 1).

Inclusion Criteria

My cancer has a KRAS gene mutation.

My condition worsened despite treatment and no other effective options are available.

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

Exclusion Criteria

Known sensitivity or contraindication to any component of study intervention

Hematologic abnormalities

I have an immune system disorder that needs long-term steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-07934040 alone or in combination with other anti-cancer therapies in 21-day or 28-day cycles

Up to 2 years

1 to 4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• PF-07934040

Trial Overview The study tests PF-07934040 alone or combined with other anti-cancer drugs (like Paclitaxel, Carboplatin) given orally or intravenously over cycles of 21 to 28 days. The goal is to determine the safety, effective dose, and effects on various advanced cancers.

How Is the Trial Designed?

Group I: Part 2b Cohort C3 Experimental Treatment 6 Interventions

Combination (PF-07934040 + Pembro + Platinum Chemo) dose escalation/expansion in 1L NSCLC (any TPS) Prescribed dose and frequency in 21-day cycles

Group II: Part 2b Cohort C2 Experimental Treatment 2 Interventions

Combination (PF-07934040 + Pembro) dose escalation/expansion in 1L NSCLC (TPS ≥ 50%) Prescribed dose and frequency in 21-day cycles

Group III: Part 2b Cohort B3 Experimental Treatment 5 Interventions

Combination (PF-07934040 + FOLFOX + Bevacizumab) dose escalation/expansion in 1L CRC Prescribed dose and frequency in 28-day cycles

Group IV: Part 2b Cohort B2 Experimental Treatment 2 Interventions

Combination (PF-07934040 + Cetuximab) dose escalation/expansion in 2-3L CRC Prescribed dose and frequency in 28-day cycles

Group V: Part 2b Cohort A2 Experimental Treatment 3 Interventions

Combination (PF-07934040 + Gemcitabine + Nab-paclitaxel) dose escalation/expansion in 1L PDAC. Prescribed dose and frequency in 28-day cycles

Group VI: Part 2a Cohort C1 Experimental Treatment 1 Intervention

Monotherapy dose expansion in 2-3L NSCLC. PF-07934040 at prescribed dose and frequency in 28-day cycles

Group VII: Part 2a Cohort B1 Experimental Treatment 1 Intervention

Monotherapy dose expansion in 2-3L CRC. PF-07934040 at prescribed dose and frequency in 28-day cycles

Group VIII: Part 2a Cohort A1 Experimental Treatment 1 Intervention

Monotherapy dose expansion in 2-3L PDAC. PF-07934040 at prescribed dose and frequency in 28-day cycles

Group IX: Part 1 Experimental Treatment 1 Intervention

PF-07934040 Monotherapy Dose Escalation PF-07934040 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

Published Research Related to This Trial

In a study of 98 patients with stage IV lung adenocarcinoma who developed resistance to gefitinib, those treated with platinum-based doublet chemotherapy showed significantly better overall survival (16.1 months) compared to those who received non-platinum chemotherapy (6.7 months).

Pemetrexed, when used in combination with platinum-based chemotherapy, was associated with a significantly better progression-free survival (6.4 months) compared to those not receiving pemetrexed (4.1 months), suggesting it may be the most effective salvage therapy after gefitinib resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment. Yang, CJ., Tsai, MJ., Hung, JY., et al.[2022]

Patients with advanced non-small-cell lung cancer who have a performance status of 2 (PS2) are often excluded from clinical trials, leading to a lack of data to inform treatment decisions for this group.

While single-agent chemotherapy is still the standard treatment for PS2 patients, emerging evidence suggests that new agents or combination therapies may be beneficial, highlighting the need for a large Phase III trial to compare these treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of performance status 2 patients with advanced non-small-cell lung cancer: what we know and what we don't know. Tartarone, A., Aieta, M.[2009]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

In a study of 83 patients with stage IV non-small-cell lung cancer (NSCLC) and BRAF mutations, there was no significant difference in progression-free survival (PFS) or overall survival when compared to controls without these mutations, indicating that BRAF mutations may not be a strong prognostic factor in NSCLC.

Despite some patients receiving targeted therapies, the study found that standard chemotherapy regimens did not show a significant difference in outcomes, suggesting that BRAF mutation status does not influence the effectiveness of chemotherapy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of non-small-cell lung cancer patients with BRAF mutations: results from the French Cooperative Thoracic Intergroup biomarkers France study. Couraud, S., Barlesi, F., Fontaine-Deraluelle, C., et al.[2020]

Recent research highlights that non-small-cell lung cancer (NSCLC) is a rapidly evolving field with many new drugs being developed, but most are tested without specific biomarker selection due to a lack of predictive knowledge.

Targeted therapies, like crizotinib for patients with ALK gene rearrangement, show that using biomarker-driven patient selection can lead to significantly better outcomes compared to standard treatments, emphasizing the need for personalized medicine in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in advanced non-small-cell lung cancer: searching for the correct clinical development. Di Maio, M., Morabito, A., Piccirillo, MC., et al.[2018]

Lung cancer remains the leading cause of cancer deaths globally, prompting the development of novel targeted therapies that focus on the specific molecular characteristics of the disease.

Current treatment for advanced non-small-cell lung cancer (NSCLC) primarily involves platinum-based combination therapy, but ongoing trials are exploring new drugs like sorafenib and sunitinib, suggesting that combining these new agents with existing treatments may enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in advanced non-small-cell lung cancer treatment. Ricciardi, S., de Marinis, F.[2015]

Non-small cell lung cancer (NSCLC) accounts for about 75% of lung cancer cases, with 5-year survival rates in the U.S. ranging from 10% to 15%, highlighting the need for effective treatments.

Combination chemotherapy regimens, particularly those including cisplatin, have shown the best response rates, with newer agents like vinorelbine and gemcitabine also demonstrating promise, achieving response rates near 50% when used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management (chemotherapy/best supportive care) of advanced-stage non-small cell lung cancer. Carney, DN.[2013]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

In a study of 72 patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status, gefitinib showed modest efficacy, with a median progression-free survival of 3.7 months and overall survival of 6.3 months.

Gefitinib was well tolerated, with 82% of patients reporting improvements or no change in quality of life, despite some experiencing grade 3/4 toxicities like rash and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent gefitinib in patients with untreated advanced non-small-cell lung cancer and poor performance status: a Minnie Pearl Cancer Research Network Phase II Trial. Spigel, DR., Hainsworth, JD., Burkett, ER., et al.[2018]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

In a retrospective study of 48 patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, the combination of gemcitabine and paclitaxel showed a partial response rate of 12.5% and a median overall survival of 6.63 months.

The treatment was generally well-tolerated, with manageable grade 3 and 4 hematologic toxicities, particularly neutropenia and anemia, but no treatment-related deaths, indicating that this regimen can be a viable second-line option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus paclitaxel as second-line chemotherapy in patients with advanced non-small cell lung cancer. Baykara, M., Coskun, U., Berk, V., et al.[2019]

For first-line treatment of stage IV non-small-cell lung cancer, a platinum-based two-drug chemotherapy is recommended for patients with good performance status (0 or 1), while a single cytotoxic drug is sufficient for those with performance status of 2.

Targeted therapies like gefitinib are recommended for patients with known EGFR mutations, while cytotoxic chemotherapy is preferred for those with negative or unknown mutation status, highlighting the importance of genetic testing in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. Azzoli, CG., Baker, S., Temin, S., et al.[2022]

The TASK study, involving 124 patients with advanced non-squamous non-small cell lung cancer (NSCLC), found that combining erlotinib with bevacizumab did not improve progression-free survival (PFS) compared to chemotherapy plus bevacizumab, with median PFS of 18.4 weeks for the erlotinib group versus 25.0 weeks for the chemotherapy group.

The study was terminated early because the combination therapy showed a higher risk of disease progression or death (hazard ratio of 2.05) and a higher incidence of death (19% for erlotinib plus bevacizumab compared to 11.5% for chemotherapy plus bevacizumab), indicating that this combination may not be a safe or effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer. Ciuleanu, T., Tsai, CM., Tsao, CJ., et al.[2015]

Citations

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NCT06447662 | A Study to Learn About the ... The purpose of this study is to learn about the safety and effects of the study medicine alone or when given together with other anti-cancer therapies.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39054462/

Pembrolizumab with platinum-based chemotherapy with or ... This trial evaluated addition of epacadostat, a potent and highly selective IDO1 inhibitor, to pembrolizumab and chemotherapy for metastatic NSCLC.

3. keytruda.com keytruda.com/non-small-cell-lung-cancer/combination-therapy-clinical-trial-results/

Advanced Nonsquamous NSCLC Combination Therapy See results of a clinical trial for a combination therapy for certain patients with advanced nonsquamous non–small cell lung cancer.

4. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) non–small cell lung cancer (NSCLC) in combination with ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33872070/

Five-Year Outcomes With Pembrolizumab Versus ... Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC ...

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A Study to Learn About the Study Medicine PF-07934040 ... The purpose of this study is to learn about the safety and effects of the study medicine alone or when given together with other anti-cancer therapies.

7. cdn.amegroups.cn cdn.amegroups.cn/journals/vats/files/journals/33/articles/11484/public/11484-PB5-1410-R2.pdf?filename=actr-04-1.pdf&t=1759165516

First-line treatment strategies and potential prognostic ... Five-Year. Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell. Lung Cancer and Programmed ...

8. merck.com merck.com/news/fda-approves-keytruda-pembrolizumab-as-adjuvant-treatment-following-surgical-resection-and-platinum-based-chemotherapy-for-patients-with-stage-ib-t2a-%E2%89%A54-centimeters-ii-or-iiia-non/

FDA Approves KEYTRUDA® (pembrolizumab) as ... Approval based on KEYNOTE-091 trial, which demonstrated a clinically meaningful improvement in disease-free survival with KEYTRUDA in these patients.