PYX-201 + Pembrolizumab for Cancer

Recruiting at 6 trial locations

Overseen By Pyxis Oncology Clinical Trial Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pyxis Oncology, Inc

Must not be taking: PD-1 inhibitors

Disqualifiers: CNS metastases, Cardiovascular disease, Active infections, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs, PYX-201 (an experimental treatment) and pembrolizumab (an immunotherapy drug), to determine their safety and effectiveness for individuals with advanced solid tumors, such as certain types of breast, gastric, and cervical cancers. Researchers aim to find the optimal dose and ensure its safety. The trial consists of two parts: one tests different doses, and the other further examines the best dose. Individuals with advanced solid tumors who have a measurable tumor and meet specific health criteria may qualify for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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 trial team or your doctor.

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

Studies have shown that PYX-201 is generally well tolerated by patients with advanced solid tumors. Safety data indicate that while some treatment-related side effects occurred, they rarely led patients to discontinue treatment. This suggests that most patients can handle the treatment without serious problems.

Pembrolizumab, a common cancer treatment, is also part of the trial. Previous uses for other conditions have shown its side effects to be well-known and generally manageable.

These findings suggest that the combination of PYX-201 and pembrolizumab is expected to be safe for most patients, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PYX-201 in combination with pembrolizumab because it offers a fresh approach to cancer treatment. Unlike most cancer therapies that primarily rely on traditional chemotherapy or targeted therapies, PYX-201 is designed to work synergistically with pembrolizumab, an immunotherapy drug, to enhance the body's immune response against cancer cells. This combination aims to improve the overall effectiveness and potentially overcome resistance seen in existing treatments. By targeting cancer cells more precisely and boosting the immune system, this treatment duo holds promise for better outcomes and fewer side effects compared to current options.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that using PYX-201 with pembrolizumab may help treat advanced solid tumors. In earlier studies, PYX-201 was effective for 50% of patients with head and neck cancer, with one patient showing no signs of cancer after treatment, and it helped control the disease in all patients. For a broader group of patients with various solid tumors, PYX-201 proved effective in 26% of cases, suggesting potential benefits for those with difficult-to-treat cancers. These findings are encouraging, especially for patients who have not succeeded with other treatments. In this trial, participants will receive PYX-201 combined with pembrolizumab, aiming to enhance the body's immune response to cancer, possibly leading to better outcomes. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including specific types of breast, gastric, cervical, and head & neck cancers. Participants must be over 18 years old with a life expectancy greater than 3 months and have an ECOG Performance Status of 0 to 1 (fully active or restricted in physically strenuous activity but ambulatory). They need proper liver, kidney, blood clotting functions and at least one measurable tumor lesion.

Inclusion Criteria

Life expectancy of >3 months, in the opinion of the Investigator.

My liver is working well.

My blood counts are within normal ranges.

Exclusion Criteria

Participants with active neuropathy of any grade per CTCAE v5.0 at Screening.

I have had a solid organ or bone marrow transplant.

I have another cancer that is getting worse or was treated in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PYX-201 to evaluate safety, tolerability, and preliminary efficacy in combination with pembrolizumab

Dose Expansion

Dose-expansion cohorts are opened based on emerging data to further inform safety, tolerability, and preliminary efficacy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• PYX-201

Trial Overview The trial is testing the combination of PYX-201 with pembrolizumab to find the safest dose for Phase 2 trials in patients with advanced solid tumors. It aims to establish the maximum tolerated dose by gradually increasing amounts until side effects become too severe.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Experimental Treatment 2 Interventions

Part 2 dose-expansion cohorts will be opened based on emerging data to further inform the safety, tolerability, and preliminary efficacy determinations as defined.

Group II: Part 1: Dose Escalation Experimental Treatment 2 Interventions

Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, and preliminary efficacy of PYX-201 in combination with pembrolizumab.

Who Is Running the Clinical Trial?

Pyxis Oncology, Inc

Lead Sponsor

Trials

4

Recruited

400+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

In the KEYNOTE-010 study involving patients with advanced NSCLC, pembrolizumab significantly improved health-related quality of life (HRQoL) scores compared to docetaxel, indicating better overall patient well-being during treatment.

Patients treated with pembrolizumab experienced less deterioration in symptoms like cough and dyspnea, and showed a significant prolongation in time to deterioration for these symptoms, particularly at the 10 mg/kg dose compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1-Expressing NSCLC. Barlesi, F., Garon, EB., Kim, DW., et al.[2020]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

In the KEYNOTE-407 study, pembrolizumab combined with chemotherapy significantly improved overall survival (17.1 months) and progression-free survival (8.0 months) compared to placebo plus chemotherapy in patients with untreated metastatic squamous non-small cell lung cancer (NSCLC).

The study also found that patients receiving pembrolizumab plus chemotherapy had a longer time before disease progression on subsequent treatments (PFS-2), supporting its use as a standard first-line therapy, despite a similar rate of serious adverse events (grade 3 to 5) between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Paz-Ares, L., Vicente, D., Tafreshi, A., et al.[2021]

Pembrolizumab (P) can be safely combined with various chemotherapy agents, including gemcitabine and liposomal doxorubicin, in patients with advanced solid tumors, as shown in a phase Ib trial involving 49 patients.

The combination treatment resulted in eight partial responses across different tumor types, indicating potential efficacy, but further studies are needed to confirm if the response duration is better than chemotherapy or immunotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Weiss, GJ., Waypa, J., Blaydorn, L., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab, a biologic agent used for treating non-small cell lung cancer, can cause immune-related adverse effects (irAEs) that may persist even after the drug is no longer detectable in the bloodstream, indicating a prolonged immune response.

A case study of a 72-year-old patient revealed that pembrolizumab's clearance rate changes from linear to non-linear after about 77 days, suggesting that current fixed dosing strategies may need to be reassessed to account for the drug's complex pharmacokinetics and the potential for prolonged toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Pharmacokinetics of pembrolizumab in a patient with stage IV non-small cell lung cancer after a single 200 mg administration. de Vries, F., Smit, AAJ., Wolbink, G., et al.[2023]

Pembrolizumab is an effective cancer treatment that works by reactivating T cells, but it can lead to various immune-related adverse events, including rare cases of synovitis.

Healthcare providers should be vigilant about the potential for pembrolizumab-induced synovitis and act quickly to treat it to prevent lasting joint damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? Mahmoud, F., Wilkinson, JT., Gizinski, A., et al.[2018]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

The PePS2 trial demonstrated that pembrolizumab can be safely administered to patients with non-small-cell lung cancer (NSCLC) and a performance status of 2, with a toxicity rate of 28% and no severe treatment-related adverse events, indicating a manageable safety profile.

Efficacy outcomes showed that 38% of first-line and 36% of subsequent-line patients experienced durable clinical benefit, with higher response rates correlating with tumor proportion scores, suggesting that pembrolizumab is effective for this underserved patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Middleton, G., Brock, K., Savage, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06795412

NCT06795412 | Study of PYX-201 in Combination With ... The primary objective of this study is to determine the recommended Phase 2 doses (RP2D(s)) and maximum tolerated dose (MTD) of PYX-201 in combination with ...

2. ir.pyxisoncology.com ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-favorable-preliminary-pyx-201-clinical

Pyxis Oncology Announces Favorable Preliminary PYX ... PYX-201 achieved a confirmed 50% ORR by RECIST 1.1 including one Complete Response and 100% Disease Control Rate in six heavily pretreated HNSCC patients.

3. onclive.com onclive.com/view/pyx-201-generates-responses-in-pretreated-advanced-hnscc-and-other-solid-tumors

PYX-201 Generates Responses in Pretreated Advanced ... PYX-201 showed a 50% ORR in HNSCC patients and 26% in the overall efficacy-evaluable population, indicating potential efficacy in heavily ...

4. pyxisoncology.com pyxisoncology.com/wp-content/uploads/Pyxis-ESMO-2025-Poster_1025eTip-PYX201-Pembro-Combo_vFinal-10.10.25.pdf

A Phase 1/2 Study of a First-in-Class Non-Cellular ... ... combination with pembrolizumab in patients with R/M HNSCC and other advanced solid tumors (PYX-201-102, NCT06795412), enrolling in Part 1. REFERENCES. 1 ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT06795412

Study of PYX-201 in Combination With Pembrolizumab ... We aim to select a dose of micvotabart pelidotin in combination with pembrolizumab by mid-year 2025 and share preliminary data from the trial in the second half ...

6. ir.pyxisoncology.com ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-portfolio-prioritization-focusing

Pyxis Oncology Announces Portfolio Prioritization ... Among patients with HNSCC, PYX-201 achieved a confirmed 50% objective response rate (ORR) based on RECIST 1.1 criteria, including one complete ...

7. synapse.patsnap.com synapse.patsnap.com/article/pyxis-oncology-reports-positive-early-phase-1-data-for-pyx-201

Pyxis Oncology Reports Positive Early Phase 1 Data for ... PYX-201 has shown a confirmed 50% objective response rate (ORR) by RECIST 1.1 in HNSCC, including a complete response and 100% Disease Control ...