CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers

Study Overview
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Brief Summary
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This is a Phase 1/1b open-label, dose escalation and dose expansion study of CPI-006, a humanized monoclonal antibody (mAb) targeting the CD73 cell-surface ectonucleotidase in adult subjects with select advanced cancers. CPI-006 will be evaluated as a single agent, in combination with ciforadenant (an oral adenosine 2A receptor antagonist), in combination with pembrolizumab (an anti-PD1 antibody), and in combination with ciforadenant and pembrolizumab.

Official Title
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A PHASE 1/1b MULTICENTER STUDY TO EVALUATE THE HUMANIZED ANTI-CD73 ANTIBODY, CPI-006, AS A SINGLE AGENT OR IN COMBINATION WITH CIFORADENANT, WITH PEMBROLIZUMAB, AND WITH CIFORADENANT PLUS PEMBROLIZUMAB IN ADULT SUBJECTS WITH ADVANCED CANCERS

Conditions
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Sarcoma, Non-Small Cell Lung Cancer, Renal Cell Cancer, Colorectal Cancer, Triple Negative Breast Cancer, Cervical Cancer, Ovarian Cancer, Pancreatic Cancer, Endometrial Cancer, Squamous Cell Carcinoma of the Head and Neck, Bladder Cancer, Metastatic Castration Resistant Prostate Cancer, Non-hodgkin Lymphoma

Intervention / Treatment
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* Drug: CPI-006
* Drug: CPI-006 + ciforadenant
* Drug: CPI-006 + pembrolizumab
* Drug: CPI-006
* Drug: CPI-006 + ciforadenant
* Drug: CPI-006 + pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. Documented incurable cancer with one of the following histologies: nonsmall cell lung cancer, renal cell cancer, triple negative breast cancer, colorectal cancer with microsatellite instability(MSI), bladder cancer, cervical cancer, uterine cancer, sarcoma, endometrial cancer, and metastatic castration resistant prostate cancer. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). For Escalation: At least 1 but not more than 5 prior systemic therapies for advanced/ recurrent or progressing disease. For Expansion: Subject must have progressed on, be refractory to, or intolerant to 1-3 prior systemic therapies. Willingness to provide tumor biopsies. Exclusion Criteria History of severe hypersensitivity reaction to monoclonal antibodies. Subjects who have received prior therapy with regimens containing cytotoxicT-lymphocyte antigen-4 (CTLA-4), programmed cell death ligand 1 (PDL1), or PD1 antagonists are NOT permitted to enroll unless all adverse events (AEs) while receiving prior immunotherapy have resolved to Grade 1 or baseline prior to screening. History of (non-infectious) pneumonitis that required steroids or subject has current pneumonitis. The use of any investigational medication or device in the 30 days prior to screening and throughout the study is prohibited. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

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
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a<br>CPI-006 | Drug: CPI-006<br>* Subjects will receive escalating doses of CPI-006 administered intravenously once every 21 days until MTD is reached or until disease progression.<br>|
| Experimental: Cohort1b<br>CPI-006 + ciforadenant | Drug: CPI-006 + ciforadenant<br>* Subjects will receive escalating doses of CPI-006 administered intravenously once every 21 days in combination with CPI-444 orally twice daily until MTD is reached for CPI-006 or until disease progression.<br>|
| Experimental: Cohort 1c<br>CPI-006 + pembrolizumab | Drug: CPI-006 + pembrolizumab<br>* Subjects will receive escalating doses of CPI-006 in combination with pembrolizumab administered intravenously once every 21 days until MTD is reached for CPI-006 or until disease progression.<br>|
| Experimental: Cohort 2a<br>CPI-006 | Drug: CPI-006<br>* Selected dose of CPI-006 administered intravenously once every 21 days until disease progression.<br>|
| Experimental: Cohort 2b<br>CPI-006 + ciforadenant | Drug: CPI-006 + ciforadenant<br>* Selected dose of CPI-006 administered intravenously once every 21 days, in combination with CPI-444 orally twice daily until disease progression.<br>|
| Experimental: Cohort 2c<br>CPI-006 + pembrolizumab | Drug: CPI-006 + pembrolizumab<br>* Selected dose of CPI-006 in combination with pembrolizumab administered intravenously once every 21 days until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) of CPI-006 as a single agent and in combination with ciforadenant and with pembrolizumab. |  | From start of treatment to end of treatment, up to 36 months | 
| Incidence of treatment-emergent adverse events as assessed by NCI CTCAE v.4.03, of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab. |  | From start of treatment to end of treatment, up to 36 months | 
| Identify the MDL(maximum dose level) of single agent CPI-006 |  | From start of treatment to end of treatment, up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of CPI-006 |  | Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days). | 
| Maximum serum concentration (Cmax) of CPI-006 |  | Day 1, 2, 8 , and 15 of Cycle 1 & 4 (each cycle is 21 days). | 
| Objective response rate per RECIST v.1.1 criteria of CPI-006 as single agent and in combination with ciforadenant and with pembrolizumab. |  | From start of treatment to end of treatment, up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, RCC, TNBC, mCRPC, CRC, Lung Cancer, Kidney Cancer, Rectal Cancer, Breast Cancer, Sarcoma, Endometrial, Pancreatic, Ovarian, SCCHN, NHL