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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: CPI-1205
* Drug: ipilimumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-1205 Combination with ipilimumab<br> | Drug: CPI-1205<br>* Administered orally<br>Drug: ipilimumab<br>* Administered intravenously<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1/2, Oncology, EZH2 Inhibitor