PRO1107 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a global, open-label, multicenter Phase 1/2 study to evaluate the safety, tolerability, PK, and antitumor activity of PRO1107 in patients with advanced solid tumors. This study consists of 2 parts, Part A: dose escalation and dose level expansion, and Part B: tumor specific expansion.

Detailed Description
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This is a Phase 1/2 study of PRO1107, a PTK7 targeted antibody-drug conjugate, to evaluate the safety, tolerability, PK, and antitumor activity of PRO1107 in patients with advanced solid tumors, including ovarian cancer, endometrial cancer, triple negative breast cancer, non-small cell lung cancer, gastroesophageal cancer, and urothelial cancer. This study consists of 2 parts, Part A: Dose Escalation and Part B: Dose Expansion. Part A may evaluate up to 7 dose levels of PRO1107 on Day 1 of a 21 day cycle by IV infusion. Part B will be initiated at a dose level based on a comprehensive analysis of safety, tolerability, clinical PK, PD and activity data from Part A in up to 4 different cohorts of up to 40 patients per cohort. Patients will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.

Official Title
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A Phase 1/2 Study of PRO1107 in Patients With Advanced Solid Tumors

Conditions
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Endometrial Cancer, Ovarian Cancer, Triple Negative Breast Cancer, GastroEsophageal Cancer, Non-small Cell Lung Cancer, Urothelial Carcinoma

Intervention / Treatment
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* Drug: PRO1107


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Pathologically confirmed diagnosis of one of the following tumor types: Ovarian cancer (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer) Endometrial cancer (any subtype excluding sarcoma) Triple negative breast cancer (TNBC) Non-small cell lung cancer (NSCLC) Gastric or gastroesophageal junction (GEJ) adenocarcinoma Esophageal squamous cell carcinoma (ESCC) Urothelial cancers (bladder, ureter, or renal pelvis) Metastatic or unresectable locally advanced, recurrent, disease not amenable to further local therapy following prior systemic therapies known to confer clinical benefit. Measurable disease at baseline as defined per RECIST, Version 1.1 (Eisenhauer et al. 2009) Willing to provide a pre-treatment tumor specimen (archival or fresh biopsy samples). ECOG performance status score 0 or 1. Exclusion Criteria Prior treatment with anti-PTK7 directed therapy. Had progressive disease as best response while on treatment with an auristatin (vedotin, pelidotin)-based antibody drug conjugate (ADC) as the most recent line of therapy (Part B only). Other malignancy within 3 years Active CNS metastases (treated, stable CNS metastases are allowed) Uncontrolled infection within 2 weeks. Positive for HBV, HCV or HIV Use of a strong P450A CYP3A inhibitor within 2 weeks Additional protocol defined inclusion/exclusion criteria may apply

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
Interventional Model Description: mTPI
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO1107<br>PRO1107 monotherapy in escalating doses in Part A and at the two recommended phase 2 doses in Part B | Drug: PRO1107<br>* Intravenous infusion of PRO1107<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Type, incidence, severity, seriousness, and relatedness of adverse events | Through end of treatment, up to approximately 1 year | 
| Laboratory abnormalities | Type, incidence, and severity of laboratory abnormalities | Through end of treatment, up to approximately 1 year | 
| Dose limiting toxicity | Incidence of dose limiting toxicities | Through end of treatment, up to approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Patients who achieve partial or complete response per RECIST v1.1 criteria | Through end of treatment, up to approximately 1 year | 
| Disease Control Rate | Patients who achieve stable disease, partial or complete response per RECIST v1.1 criteria | Through end of treatment, up to approximately 1 year | 
| Progression-free survival | Time from start of treatment to first documented disease progression or death | Up to approximately 18 months | 
| Duration of objective response | Time from the first documentation of an objective tumor response (CR or PR) to the first documented tumor progression or death | From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months | 
| Pharmacokinetic parameter AUC for PRO1107 | Measure of PRO1107 area under the concentration-time curve (AUC) in plasma. | Varying timepoints through end of treatment, up to approximately 1 year | 
| Pharmacokinetic parameter Cmax for PRO1107 | Measure of the maximum concentration (Cmax) of PRO1107 in plasma. | Varying timepoints through end of treatment, up to approximately 1 year | 
| Pharmacokinetic parameter Tmax for PRO1107 | Measure of the time to maximum concentration (Tmax) of PRO1107 in plasma. | Varying timepoints through end of treatment, up to approximately 1 year | 
| Pharmacokinetic parameter t1/2 for PRO1107 | Measure of apparent terminal half-life (t1/2) of PRO1107 in plasma. | Varying timepoints through end of treatment, up to approximately 1 year | 
| Pharmacokinetic parameter Ctrough for PRO1107 | Measure of the trough concentration (Ctrough) of PRO1107 in plasma. | Varying timepoints through end of treatment, up to approximately 1 year |