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

• ClinicalTrials.gov Identifier: NCT03525795
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2018
• Last Update Posted: January 7, 2019
• Sponsor: Constellation Pharmaceuticals
• Information provided by (Responsible Party): Constellation Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: CPI-1205; Drug: ipilimumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 14, 2017
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Objective response rate [ Time Frame: 1 year ]
   The rate of confirmed iCR + iPR
2. Clinical Benefit Rate [ Time Frame: 3 months ]
   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. Time to response [ Time Frame: 1 year ]
   The time from day (D) 1 of treatment to the date of first response as determined by RECIST 1.1 and iRECIST criteria
4. Duration of Response [ Time Frame: 1 year ]
   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
5. Duration of treatment [ Time Frame: 1 year ]
   The time from D1 of treatment until the date treatment is discontinued for any reason
6. Progression free survival [ Time Frame: 6 months ]
   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
7. Adverse Events [ Time Frame: 1 year ]
   AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Michigan

START Midwest

Grand Rapids, Michigan, United States, 49546

United States, Texas

The University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030

South Texas Oncology & Hematology

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Constellation Pharmaceuticals

Investigators

• Study Director: Debbie Johnson; Constellation Pharmaceuticals

More Information

• Responsible Party: Constellation Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03525795 History of Changes
• Other Study ID Numbers: 1205-202
• First Posted: May 16, 2018
• Last Update Posted: January 7, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Constellation Pharmaceuticals:

Phase 1/2; Oncology; EZH2 Inhibitor

Additional relevant MeSH terms:

Neoplasms; 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action