Study of PYX-106 in Solid Tumors

Study Overview
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Brief Summary
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The primary objective of this study is to determine the recommended dose(s) of PYX-106 in participants with relapsed/refractory solid tumors.

Official Title
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A First-in-Human, Open-label, Multicenter, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PYX-106 in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: PYX-106


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with histologically or cytologically confirmed solid tumors who have relapsed, been non-responsive, or have developed disease progression through standard therapy. Histologically or cytologically confirmed solid tumors (see details below): For the dose escalation, the following solid tumors are allowed in participants who have developed disease progression through standard therapy and in participants for whom standard of care therapy that prolongs survival is unavailable or unsuitable, which include non-small cell lung cancer without driver mutations/translocations, breast cancer, endometrial cancer, thyroid cancer, kidney cancer, cholangiocarcinoma, bladder cancer, colorectal cancer, and head and neck squamous cell carcinoma. Clinical sites must provide archived tissue or conduct fresh tumor biopsy (formalin-fixed paraffin-embedded [FFPE]; enough to create a minimum of 14 slides). Fresh biopsy pre-treatment is preferred, archival tissue (the most recent available) is acceptable if fresh biopsy is not performed at Screening. Both fresh and archival tissue samples must be collected by core needle biopsy or surgical resection. Fine needle aspirates are not permitted. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 criteria (by local Investigator). Participant must have radiographic evidence of disease progression based on RECIST criteria following the most recent line of treatment. Life expectancy of >3 months, in the opinion of the Investigator. Exclusion Criteria: 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; other adequately treated Stage 1 or 2 cancers currently in complete remission; any other cancer that has been in complete remission for >2 years or cancer of low risk of recurrence; or any treated or monitored indolent cancer that is unlikely to cause mortality in 5 years. Known symptomatic brain metastases requiring >10 mg/day of prednisolone (or its equivalent) at the time of signing informed consent. Continuance of toxicities due to prior anti-cancer agents that do not recover to Grade 1 prior to start of PYX-106 treatment, except for alopecia or endocrine deficiencies treated with stable hormone replacement therapy. Presence of Grade ≥2 peripheral neuropathy. Major surgery within 4 weeks prior to the start of PYX-106 treatment, as defined by the Investigator. Received palliative radiation therapy within 14 days prior to the start of PYX-106 treatment. Received a live vaccine within 28 days prior to the first dose of study treatment and while participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PYX-106 Dose Escalation<br>Participants will receive escalating doses of PYX-106 to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of PYX-106, and to determine the recommended dose(s). | Drug: PYX-106<br>* Intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) |  | Day 1 to Day 28 | 
| Number of Participants Who Experience an Adverse Event (AE) | Type, incidence, seriousness and causality of AEs based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Any clinically significant changes in clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be recorded as AEs. | Day 1 up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Time to Maximum Concentration (Tmax) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Area Under the Time Concentration Curve from Time 0 to the Last Quantifiable Concentration (AUC0-t) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Area Under the Time Concentration Curve from Time 0 to the End of the Dosing Interval (AUCtau) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Area Under the Time Concentration Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Half Life (t1/2) of PYX-106 |  | Day 1 up to approximately 2 years | 
| Objective Response Rate (ORR) |  | Day 1 up to approximately 2 years | 
| Duration of Response (DOR) |  | Day 1 up to approximately 2 years | 
| Progression Free Survival (PFS) |  | 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 | 
| Overall Survival (OS) |  | Day 1 up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Advanced Solid Tumors, PYX-106, Relapsed Solid Tumors, Refractory Solid Tumors