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

Recruiting at23 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Pfizer

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pneumonitis, Autoimmune disease, GI disease, others

No Placebo Group

Breakthrough Therapy

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 alone or when given together with other anti-cancer therapies. This study also aims to find the best dose. This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that: * are advanced (cancer that doesn't disappear or stay away with treatment) and * have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers). 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 (a part of large intestine) or rectum grow out of control. Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels. All participants in this study will take the study medication (PF-07934040) as pill by mouth twice a day repeating for 21-day or 28-day cycles. Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07934040 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at various times (depending on the treatment) during the 21-day or 28-day cycle. Participants can continue to take the study medication (PF-07934040) and the combination anti-cancer therapy until their cancer is no longer responding. 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, they will come into the clinic between 1 to 4 times in each 21-day or 28-day cycle. After they have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing.

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.

What data supports the effectiveness of the drug PF-07934040 for non-small cell lung cancer?

The research suggests that combination chemotherapy, which includes drugs like paclitaxel and gemcitabine, has shown promise in treating non-small cell lung cancer, with response rates approaching 50% when used with other effective agents. This indicates that combining PF-07934040 with other anti-cancer therapies might also be effective. ^{1 2 3 4 5}

What safety information is available for PF-07934040 and similar targeted cancer therapies?

Targeted cancer therapies, like PF-07934040, can cause side effects affecting the skin, stomach, lungs, and heart. These treatments have been linked to an increased risk of serious and fatal adverse events compared to placebo, highlighting the need for careful monitoring. ^{1 6 7 8 9}

What makes the drug PF-07934040 unique for treating non-small cell lung cancer?

PF-07934040 is unique because it is being tested in combination with other anti-cancer therapies, potentially offering a novel approach compared to standard doublet chemotherapy regimens. This combination could improve survival rates beyond the typical outcomes seen with existing treatments. ^{4 10 11 12 13}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Known sensitivity or contraindication to any component of study intervention

Hematologic abnormalities

Trial Timeline

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

Treatment Details

Interventions

• PF-07934040 (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2018]

2. Thailand pubmed.ncbi.nlm.nih.gov

Gemcitabine plus paclitaxel as second-line chemotherapy in patients with advanced non-small cell lung cancer. [2019]

3. New Zealand 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. [2022]

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

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

5. England 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. [2009]

6. Switzerland 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. [2023]

7. India 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. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

New agents in advanced non-small-cell lung cancer treatment. [2015]

9. Ireland 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. [2015]

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

Triplet combination chemotherapy and targeted therapy regimens. [2005]

11. England 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. [2020]

12. England pubmed.ncbi.nlm.nih.gov

New drugs in advanced non-small-cell lung cancer: searching for the correct clinical development. [2018]

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

American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. [2022]