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

NCT03525795 | Completed Phase 1 FDA Drug

• 1 other identifier: 1205-202
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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

Conditions

Advanced Solid Tumors

Keywords

Phase 1/2; Oncology; EZH2 Inhibitor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Objective response rate

  1 year

• Clinical Benefit Rate

  3 months

• Time to response

  1 year

• Duration of Response

  1 year

• Duration of treatment

  1 year

Study Arms (1)

CPI-1205 Combination with ipilimumab

EXPERIMENTAL

Drug: CPI-1205; Drug: ipilimumab

Interventions

CPI-1205 DRUG

Administered orally

CPI-1205 Combination with ipilimumab

ipilimumab DRUG

Administered intravenously

CPI-1205 Combination with ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Relapsed following or progressed through standard therapy
• Have a disease for which no standard effective therapy exists (i.e., a therapy that demonstrates a significant increase in survival)
• 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:
• Cohort A: unresectable or metastatic melanoma
• Cohort B: metastatic NSCLC
• Cohort C: advanced or metastatic (stage 4) RCC
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Constellation Pharmaceuticals: lead

Study Sites (3)

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Oncology & Hematology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

(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; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 16, 2018
• Study Start: December 14, 2017
• Primary Completion: June 12, 2019
• Study Completion: June 12, 2019
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

US (3)