Phase 1/2 Study of PYX-201 in Combination With Pembrolizumab in Advanced Solid Tumors

A Phase 1/2, Open-label, Global, Multicenter, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

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 pembrolizumab for participants with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: PYX-201; Drug: pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pyxis Oncology Clinical Trial Team; Phone Number: 617-453-3596; Email: clinicaltrials@pyxisoncology.com

Study Locations

• France
  • Bordeaux, France, 33075
    • Recruiting
    • Hopital Saint - Andre - CHU de Bordeaux
  • Lyon, France, 69373
    • Recruiting
    • Centre Léon Bérard
  • Marseille, France, 13385
    • Recruiting
    • Hopital de la Timone
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • START Madrid - Hospital Universitario Fundacion Jimenez Diaz
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
• United States
  • California
    • San Diego, California, United States, 92093
      • Recruiting
      • University Of California San Diego
    • Santa Monica, California, United States, 90403
      • Recruiting
      • Sarcoma Oncology Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas - M.D. Anderson Cancer Center
    • Houston, Texas, United States, 77054
      • Recruiting
      • NEXT Oncology Houston
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Histologically or cytologically confirmed advanced solid tumors, including first-line (1L) head and neck squamous cell carcinoma (HNSCC), advanced or metastatic triple negative breast cancer (TNBC), hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative breast cancer (HER2- BC), gastric cancer (GC), cervical cancer, and second-line and higher (2L+) HNSCC.
2. Male or non-pregnant, non-lactating female participants age ≥18 years.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.
4. Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
5. Life expectancy of >3 months, in the opinion of the Investigator.
6. Adequate hematologic function.
7. Adequate hepatic function.
8. Adequate renal function.
9. Adequate coagulation profile.
10. Clinical sites must conduct fresh tumor biopsy or provide participant's archived tumor tissue sample.

Exclusion Criteria

1. Known additional malignancy that is progressing or has required active treatment within the past 2 years.
2. Have any active central nervous system (CNS) metastases and/or carcinomatous meningitis.
3. Significant cardiovascular disease within 6 months prior to start of study drug.
4. Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of study drug.
5. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
6. Failure to recover to Baseline severity or National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 from acute non-hematologic toxicity due to previous therapy, prior to Screening.
7. Participants with Grade >1 neuropathy of any grade per CTCAE v5.0 and/or receiving treatment for neuropathy at Screening.
8. History of uncontrolled diabetes mellitus.
9. Participants with immunodeficiency or active autoimmune disease that is contraindicated for pembrolizumab.
10. Participants with a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
11. Prior solid organ or bone marrow progenitor cell transplantation.
12. Prior high-dose chemotherapy requiring stem cell rescue.
13. Previously received treatment with a programmed death-1 (PD-1)/L1 inhibitor any prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor.
14. Severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients and/or PYX-201 and/or any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, and preliminary efficacy of PYX-201 in combination with pembrolizumab.	Drug: PYX-201; Intravenous (IV) infusion.; Drug: pembrolizumab; IV infusion.; Other Names: KEYTRUDA®
Experimental: Part 2: Dose Expansion; Part 2 dose-expansion cohorts will be opened based on emerging data to further inform the safety, tolerability, and preliminary efficacy determinations as defined.	Drug: PYX-201; Intravenous (IV) infusion.; Drug: pembrolizumab; IV infusion.; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants who Experience a Dose-Limiting Toxicity (DLT)	Day 1 to Day 21
Number of Participants who Experience an Adverse Event (AE)	Up to approximately 2 years
Number of Participants who Experience Clinically Significant Changes in Clinical Laboratory Parameters	Up to approximately 2 years
Number of Participants who Experience Clinically Significant Changes in Vital Signs	Up to approximately 2 years
Number of Participants who Experience Clinically Significant Changes in electrocardiogram (ECG) Parameters	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Day 1 up to approximately 2 years
Duration of Response (DOR)	Day 1 up to approximately 2 years
Disease Control Rate (DCR)	Day 1 up to approximately 2 years
Time to Response	Day 1 up to approximately 2 years
Clinical Benefit Rate (CBR)	Day 1 up to approximately 2 years
Maximum Observed Concentration (Cmax) of PYX-201	Day 1 up to approximately 2 years
Time to Maximum Concentration (Tmax) of PYX-201	Day 1 up to approximately 2 years
Clearance (CL) of PYX-201	Day 1 up to approximately 2 years
Area Under the Concentration-time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-t) of PYX-201	Day 1 up to approximately 2 years
Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201	Day 1 up to approximately 2 years
Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-201	Day 1 up to approximately 2 years
Half-Life (t½) for Antibody-drug Conjugate (ADC)	Day 1 up to approximately 2 years
Half-Life (t½) for Total Antibody (tAb)	Day 1 up to approximately 2 years
Half-Life (t½) for Free Payload	Day 1 up to approximately 2 years
Incidence of Anti-PYX-201 Antibodies	Day 1 up to approximately 2 years

Collaborators and Investigators

• Sponsor: Pyxis Oncology, Inc
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): December 6, 2027
• Study Completion (Estimated): December 6, 2027

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): January 28, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pembrolizumab; Advanced Solid Tumors; PYX-201
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: PYX-201-102; KEYNOTE-G17 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-G17 (Other Identifier: Merck Sharp & Dohme LLC); 2025-521828-30-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No