Clinical trial NCT05720117: Study of PYX-201 in Solid Tumors
Official title: A First-in-Human, Open-label, Multicenter, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Advanced Solid Tumor
Keywords: Relapsed/refractory Solid Tumor
PYX-201
Lead sponsor: Pyxis Oncology, Inc
Sponsor class: INDUSTRY
First posted: 2023-02-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to determine the recommended dose(s) of PYX-201 for participants with relapsed/refractory (R/R) solid tumors, and to determine the objective response rate (ORR) in participants treated with PYX-201 as a single agent.


Eligibility criteria: Inclusion

1. Histologically or cytologically confirmed solid tumors including locally advanced/metastatic NSCLC, HR+ and HER2- breast cancer, HR- and HER2-positive breast cancer, TNBC, HNSCC, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma (PDAC), sarcomas, hepatocellular carcinoma (HCC), kidney cancer, cervical cancer and endometrial cancer.
2. Male or non-pregnant, non-lactating female participants age ≥18 years.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1.
4. Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Life expectancy of \>3 months, in the opinion of the Investigator.
6. Corrected QTcF \<470 msec.
7. Adequate hematologic function.
8. Adequate hepatic function.
9. Adequate renal function.
10. Adequate coagulation profile.
11. Clinical sites must conduct fresh tumor biopsy or provide participant's archived tumor tissue sample.

Exclusion

1. History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, noninvasive bladder cancer.
2. Known symptomatic brain metastases.
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 Grade ≤1 NCI-CTCAE v5.0 from acute non-hematologic toxicity.
7. Participants with NCI-CTCAE v5.0 Grade \>1 neuropathy of any etiology.
8. Prior solid organ or bone marrow progenitor cell transplantation.
9. Prior high-dose chemotherapy requiring stem cell rescue.
10. Received systemic anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to the start of study drug.
11. Palliative radiation therapy within 14 days prior to the start of study drug.
12. Previously received extra domain B splice variant of fibronectin (EDB+FN) targeting treatments at any time prior to the start of PYX-201 treatment.
13. History of uncontrolled diabetes mellitus.
14. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
15. Participants with corneal epithelial disease, with the exception of mild punctate keratopathy
16. Participants with the best-corrected visual acuity in the worst-seeing eye worse than 20/100 (Snellen equivalent).

Primary outcomes:
measure: Part 1: Number of Participants who Experience a Dose-limiting Toxicity (DLT)
timeFrame: Day 1 to Day 21
measure: Part 1: Number of Participants who Experience an AE
timeFrame: Up to approximately 3 years
measure: Part 2: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Part 1: Maximum Observed Concentration (Cmax) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Time to Maximum Concentration (Tmax) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Clearance (CL) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Area Under the Concentration-time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-t) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Area Under the Concentration-time Curve Over the Dosing Interval (AUCtau) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1:Half-life (t½) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum
timeFrame: Day 1 up to approximately 2 years
measure: Part 1: ORR
timeFrame: Up to approximately 3 years
measure: Part 1:Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Part 1:Progression-free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Part 1:Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years
measure: Part 1:Time to Response (TTR)
timeFrame: Up to approximately 3 years
measure: Part 1:Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Part 1:Number of Participants With Anti-drug Antibodies to PYX-201
timeFrame: Up to approximately 2 years
measure: Part 2: DOR
timeFrame: Up to approximately 2 years
measure: Part 2: Clinical Benefit Rate
timeFrame: Up to approximately 2 years
measure: Part 2: Median Progression-free Survival (mPFS)
timeFrame: Up to approximately 4 years
measure: Part 2: DCR
timeFrame: Up to approximately 2 years
measure: Part 2: TTR
timeFrame: Up to approximately 2 years
measure: Part 2: Median Overall Survival (mOS)
timeFrame: Up to approximately 4 years
measure: Part 2: Cmax of PYX-201
timeFrame: Up to approximately 2 years
measure: Part 2: Tmax of PYX-201
timeFrame: Up to approximately 2 years
measure: Part 2: Trough Concentration of PYX-201
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants who Experience an AE
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Denver
country: United States
facility: SCRI - HealthOne Denver
state: Colorado
city: Sarasota
country: United States
facility: SCRI - Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Madrid
country: Spain
facility: START Madrid - Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: València
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
References: