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

Sponsor

Constellation Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03525795

Collaborator

(none)

Enrollment

Locations

Arm

17.9

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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.

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: CPI-1205 Drug: ipilimumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

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 :

Dec 14, 2017

Actual Primary Completion Date :

Jun 12, 2019

Actual Study Completion Date :

Jun 12, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: CPI-1205 Combination with ipilimumab

Drug: CPI-1205

Administered orally

Drug: ipilimumab

Administered intravenously

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Objective response rate [1 year]
The rate of confirmed iCR + iPR
Clinical Benefit Rate [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
Time to response [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
Duration of Response [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
Duration of treatment [1 year]
The time from D1 of treatment until the date treatment is discontinued for any reason
Progression free survival [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
Adverse Events [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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
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

	Site	City	State	Country	Postal Code
1	START Midwest	Grand Rapids	Michigan	United States	49546
2	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
3	South Texas Oncology & Hematology	San Antonio	Texas	United States	78229