Clinical trial NCT06795412: Study of PYX-201 in Combination With Pembrolizumab in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumours
Keywords: Advanced Solid Tumours
PYX-201
Pembrolizumab
Lead sponsor: Pyxis Oncology, Inc
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2025-01-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 Tumours (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. Known 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 active neuropathy of any grade per CTCAE v5.0 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.

Primary outcomes:
measure: Number of Participants who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 21
measure: Number of Participants who Experience an Adverse Event (AE)
timeFrame: Up to approximately 2 years
measure: Number of Participants who Experience Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: Up to approximately 2 years
measure: Number of Participants who Experience Clinically Significant Changes in Vital Signs
timeFrame: Up to approximately 2 years
measure: Number of Participants who Experience Clinically Significant Changes in electrocardiogram (ECG) Parameters
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Day 1 up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Day 1 up to approximately 2 years
measure: Disease Control Rate (DCR)
timeFrame: Day 1 up to approximately 2 years
measure: Time to Response
timeFrame: Day 1 up to approximately 2 years
measure: Clinical Benefit Rate (CBR)
timeFrame: Day 1 up to approximately 2 years
measure: Maximum Observed Concentration (Cmax) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Time to Maximum Concentration (Tmax) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Clearance (CL) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Area Under the Concentration-time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-t) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-201
timeFrame: Day 1 up to approximately 2 years
measure: Half-Life (t½) for Antibody-drug Conjugate (ADC)
timeFrame: Day 1 up to approximately 2 years
measure: Half-Life (t½) for Total Antibody (tAb)
timeFrame: Day 1 up to approximately 2 years
measure: Half-Life (t½) for Free Payload
timeFrame: Day 1 up to approximately 2 years
measure: Incidence of Anti-PYX-201 Antibodies
timeFrame: Day 1 up to approximately 2 years
Other outcomes:
Locations:
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: