A Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts

Study Overview
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Brief Summary
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This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Expansion Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, and PK (pharmacokinetics). The Dose Escalation Phase is complete and no longer enrolling. The Dose Expansion Phase has two cohorts: one cohort for the study of PT-112 in patients with thymoma and thymic carcinoma (Cohort A), and one cohort for the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC) (Cohort D).

Detailed Description
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This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase, and the Dose Expansion Phase The Dose Escalation Phase and the Dose Expansion Thymoma Cohort are complete and no longer enrolling. The Dose Expansion Phase of the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC) is open and enrolling.

Official Title
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A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts

Conditions
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CRPC, Advanced Solid Tumors, mCRPC, Metastatic Castrate-resistant Prostate Cancer, PT-112, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site

Intervention / Treatment
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* Drug: PT-112 Injection


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male >/= 18 years of age Histologically or cytologically confirmed adenocarcinoma of the prostate. Document current evidence of metastatic castration-resistant prostate cancer (mCRPC), where metastatic status is defined as having documented metastatic lesion(s) on either bone scan or CT/MRI scan. Patients who have received at least three prior intended life-prolonging therapies for metastatic disease. Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1. Progressive disease, either measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or PCWG3 or by informative tumor marker(s). Adequate organ function based on laboratory values. If there is a known history of brain metastases, either treated or untreated, the disease must be stable. Key Exclusion Criteria: Any cytotoxic chemotherapy within 21 days prior to initiation of study drug. Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy, immunosuppressive therapy, corticosteroids, or growth factor treatment within 14 days prior to initiation of study drug. Bone marrow reserve which is not adequate for participation in this trial. Radiotherapy within 14 days prior to baseline. Fraction of radiotherapy to >25 % of active bone marrow. Major surgery within 28 days prior to initiation of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects enrolled in Cohort D Part 2 will be randomized.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: PT-112 injection<br>Arm 1: PT-112 Injection, administered by intravenous infusion, biweekly 360 mg/m2 | Drug: PT-112 Injection<br> <br> * Other names: PT-112;|
| Experimental: Arm 2: PT-112 injection<br>Arm 2: PT-112 Injection, administered by intravenous infusion, biweekly 250 mg/m2 | Drug: PT-112 Injection<br> <br> * Other names: PT-112;|
| Experimental: Arm 3: PT-112 injection<br>Arm 3: PT-112 Injection, administered by intravenous infusion, 360 mg/m2 for two doses, 250 mg/m2 for subsequent doses | Drug: PT-112 Injection<br> <br> * Other names: PT-112;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial design: Comparison of two dose levels, administered on Days 1 and 15 of each 28-day cycle: | [ ] Define the recommended dose level for PT-112 for pivotal studies based on the risk/benefit ratio across Arms 1, 2 and 3. Cohort D only | 28-day cycle | 
| Modified design: Define the recommended dose and schedule for PT-112 for pivotal studies | Define the recommended dose and schedule for PT-112 for pivotal studies. Cohort D only | 28-day cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate by disease manifestation, evaluated using PCWG3-modified RECIST criteria | Cohort D only | up to 24 months | 
| Objective Response Rate (ORR) in patients with RECIST-measurable disease, evaluated using PCWG3-modified RECIST criteria | Cohort D only | up to 24 months | 
| Median duration of response (DOR) as defined by PCWG3-modified RECIST criteria | Cohort D only | up to 24 months | 
| Percentage of patients achieving PSA50 as defined by PCWG3 criteria | Cohort D only | up to 24 months | 
| Percentage of patients who are CTC nonzero at baseline and with 0 CTCs/mL in one or more post-baseline samples (i.e., CTC0) | Cohort D only | up to 24 months | 
| Percentage of patients who have ≥ 3 CTCs at baseline and ≤ 3 CTCs in one or more post-baseline samples (i.e., CTC conversion) | Cohort D only | up to 24 months | 
| Median radiographic progression free survival (rPFS) by PCWG3 criteria | Cohort D only | up to 24 months | 
| Median overall survival (OS) | Cohort D only | up to 24 months | 
| Time to PSA progression by PCWG3 criteria | Cohort D only | up to 24 months | 
| Change in disease related pain based on ACS Daily Pain Diary assessment | Cohort D only | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PT-112