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

Conditions

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

Keywords

NSCLC, RCC, TNBC, mCRPC, CRC, Lung Cancer, Kidney Cancer, Rectal Cancer, Breast Cancer, Sarcoma, Endometrial, Pancreatic, Ovarian, SCCHN, NHL

Brief summary

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.

Richard A. Miller, Jason J. Luke, Shenshen Hu, Suresh Mahabhashyam, William B. Jones et al. (9 authors)

Journal for ImmunoTherapy of Cancer2022-12-0122 citations

10.1136/jitc-2022-005802

701 Activating CD73 on B cells as a target for immunotherapy of COVID-19 and viral associated cancers: clinical activity in human papilloma virus positive (HPV) head and neck squamous cell cancers (HNSCC)

Jason J. Luke, Jaime R. Merchan, Brett Hughes, Jeffrey A. Sosman, Abhishek Tripathi et al. (15 authors)

Regular and Young Investigator Award Abstracts2021-11-013 citations

10.1136/jitc-2021-sitc2021.701

Immunobiology, preliminary safety, and efficacy of CPI-006, an anti-CD73 antibody with immune modulating activity, in a phase 1 trial in advanced cancers.

Jason J. Luke, John D. Powderly, Jaime R. Merchan, Minal Barve, Andrew Hotson et al. (11 authors)

Journal of Clinical Oncology2019-05-2044 citations

10.1200/jco.2019.37.15_suppl.2505

A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers.

Mehrdad Mobasher, Richard A. Miller, Long Kwei, Deborah Strahs, Vaijayanti Das et al. (12 authors)

Journal of Clinical Oncology2019-05-208 citations

10.1200/jco.2019.37.15_suppl.tps2646

Interventions

DRUGCPI-006

Subjects will receive escalating doses of CPI-006 administered intravenously once every 21 days until MTD is reached or until disease progression.

DRUGCPI-006 + ciforadenant

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.

DRUGCPI-006 + pembrolizumab

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.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. 2. 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. 3. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). 4. 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. 5. Willingness to provide tumor biopsies.

Exclusion criteria

1. History of severe hypersensitivity reaction to monoclonal antibodies. 2. 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. 3. History of (non-infectious) pneumonitis that required steroids or subject has current pneumonitis. 4. The use of any investigational medication or device in the 30 days prior to screening and throughout the study is prohibited. 5. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.

Design outcomes

Primary

Measure	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

Measure	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

Countries

Australia, United States

Outcome results

None listed