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

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.


Eligibility 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