ORIOn-E: A Study Evaluating CPI-1205 in Patients With Advanced Solid Tumors

A Phase 1 Study of CPI-1205 With Ipilimumab in Patients With Advanced Solid Tumors Followed by a Phase 2 Basket Study of CPI-1205 With Ipilimumab in Selected Tumor Types Previously Treated With PD-1 or PD-L1 Inhibitors

This is a Phase 1/2, multi-center, open-label study of CPI-1205 + ipilimumab in patients with histologically or cytologically confirmed advanced solid tumors. This study is designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CPI-1205 + ipilimumab in patients with advanced solid tumors. Patients in Phase 2 will be treated at the RP2D of CPI-1205 + ipilimumab.

This study was stopped prior to proceeding to Phase 2; no patients were enrolled in Phase 2.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: CPI-1205; Drug: ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas - MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Oncology & Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Diagnosis and Prior Treatment:

• Phase 1: Patients with histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor who meet one of the following criteria:

  1. Relapsed following or progressed through standard therapy
  2. Have a disease for which no standard effective therapy exists (i.e., a therapy that demonstrates a significant increase in survival)
  3. Not a candidate for standard effective therapy NOTE: In men with prostate cancer, baseline testosterone levels must also be ≤50ng/dL (≤ 2.0nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study.

• Phase 2: Patients with histologically or cytologically confirmed diagnosis of one of the following and with progressive disease during or after treatment with a PD-1 or PD-L1-inhibitor:

  1. Cohort A: unresectable or metastatic melanoma
  2. Cohort B: metastatic NSCLC
  3. Cohort C: advanced or metastatic (stage 4) RCC
  4. Cohort D: unresectable or metastatic urothelial carcinoma (urethra, bladder, ureters, or renal pelvis)
• If patient has known brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs).
• Phase 1: patients may have measurable or non-measurable disease; measurable disease via RECIST 1.1 is required for Phase 2 patients
• Recovery from recent surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1 (other than alopecia); ≤ Grade 2 neuropathy allowed
• Demonstrate adequate organ function
• Ability to swallow and retain oral medications

Exclusion Criteria:

• Carcinomatous meningitis
• Prior treatment with CTLA-4 inhibitor
• Phase 2 Cohort: ocular melanoma
• Experienced an immune-related adverse event (irAE) that led to permanent discontinuation of prior immunotherapy
• History of severe hypersensitivity reaction to treatment with another monoclonal antibody
• History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; NOTE: history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Known history of human immunodeficiency virus (HIV) (HIV1/2 antibodies)
• Gastrointestinal (GI) disorder that negatively affects absorption

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPI-1205 Combination with ipilimumab	Drug: CPI-1205; Administered orally; Drug: ipilimumab; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Frequency of Dose-limiting toxicities (DLTs)	The RP2D will be selected based on the PK, pharmacodynamics and overall tolerability of the regimen, but will not exceed the MTD.	1 year
Phase 2: Objective response rate	The rate of confirmed complete responses (CR) + partial responses (PR) as determined by RECIST 1.1 criteria	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	The rate of confirmed iCR + iPR	1 year
Clinical Benefit Rate	The rate of CR + PR + stable disease (SD) after 3 months of treatment as determined by RECIST 1.1 criteria and as the rate of iCR + iPR + iSD after 3 months of treatment by iRECIST criteria	3 months
Time to response	The time from day (D) 1 of treatment to the date of first response as determined by RECIST 1.1 and iRECIST criteria	1 year
Duration of Response	The time from measurement criteria are first met for CR/PR or iCR/iPR (whichever is first recorded) until the date of recurrence or progressive disease as determined by RECIST 1.1 and iRECIST criteria	1 year
Duration of treatment	The time from D1 of treatment until the date treatment is discontinued for any reason	1 year
Progression free survival	The time from D1 of treatment to the date of progression or death, whichever occurs first with progressive disease as determined by RECIST 1.1 and iRECIST criteria	6 months
Adverse Events	AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).	1 year

Collaborators and Investigators

• Sponsor: Constellation Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2017
• Primary Completion (Actual): June 12, 2019
• Study Completion (Actual): June 12, 2019

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Oncology; Phase 1/2; EZH2 Inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab; (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide
• Other Study ID Numbers: 1205-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No