Study of PYX-201 in Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to determine the recommended dose(s) of PYX-201 for participants with relapsed/refractory (R/R) 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

Conditions
-----------------
Solid Tumor, Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: PYX-201


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or non-pregnant, non-lactating female participants age ≥18 years. 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 (according to the Investigator), which include non-small cell lung cancer (NSCLC), locally advanced/metastatic breast cancer, hormone receptor positive breast cancer and human epidermal growth factor receptor 2 negative breast cancer, ovarian cancer, thyroid cancer, pancreatic ductal adenocarcinoma (PDAC), soft tissue sarcoma (STS), hepatocellular carcinoma (HCC), and kidney cancer. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. Participant must have at least 1 measurable lesion Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (by local Investigator) except participants with bone-only metastatic breast cancer (mBC) who can be enrolled without measurable disease. 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. Clinical sites must provide participants' archived tissue or conduct fresh tumor biopsy. 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. 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, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for >2 years or cancer of low risk of recurrence if agreed to by the medical monitor, except 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. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of PYX-201 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥4 weeks after treatment. Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment at the start of PYX-201 treatment. Major surgery within 4 weeks prior to the start of PYX-201 treatment, as defined by the Investigator. Prior solid organ or bone marrow progenitor cell transplantation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PYX-201 Dose Escalation<br>Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of PYX-201. | Drug: PYX-201<br>* Intravenous (IV) infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience a Dose-limiting Toxicity (DLT) | DLT is defined as (1) an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs after the treatment with PYX-201 and (2) meets any of the predefined criteria outlined in the protocol. | Day 1 to Day 21 | 
| Number of Participants who Experience an Adverse Event (AE) | Type, incidence, seriousness, relationship to study treatment and severity of AEs, including serious AEs and AEs at Grade 3 or above, 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. | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum |  | Day 1 up to approximately 2 years | 
| Time to Maximum Concentration (tmax) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum |  | Day 1 up to approximately 2 years | 
| Clearance (CL) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum |  | 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 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum |  | Day 1 up to approximately 2 years | 
| 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 |  | Day 1 up to approximately 2 years | 
| 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 |  | Day 1 up to approximately 2 years | 
| Half-life (t½) of PYX-201 Antibody-drug Conjugate, Total Antibody, Free Payload and Associated Metabolites in Serum |  | Day 1 up to approximately 2 years | 
| Objective Response Rate (ORR) |  | Up to approximately 3 years | 
| Duration of Response (DOR) |  | Up to approximately 3 years | 
| Progression-free Survival (PFS) |  | Up to approximately 3 years | 
| Disease Control Rate (DCR) |  | Up to approximately 3 years | 
| Time to Response |  | Up to approximately 3 years | 
| Overall Survival (OS) |  | Up to approximately 3 years | 
| Number of Participants With Anti-drug Antibodies to PYX-201 |  | Up to approximately 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Relapsed/refractory Solid Tumor, PYX-201