Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma

MEL-212: A Phase I Proof-of-Concept Study of CBL0137 (Curaxin) Combined With Ipilimumab and Nivolumab Therapy in Locally Advanced or Metastatic Melanoma

Phase I, open label, dose-escalation, and safety study designed to assess the safety and biologic activity of the investigational agent CBL0137 in combination with standard of care drugs, ipilimumab and nivolumab in sequential cohorts of adult patients with locally advanced and metastatic melanoma who are candidates for immune checkpoint blockade and have tumors accessible for serial biopsies.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Melanoma
• Intervention / Treatment: Drug: CBL0137; Drug: Ipilimumab; Drug: Nivolumab

Detailed Description

The primary objectives will be Initial assessment of safety and tolerability of the combination of CBL0137 with Nivolumab and Ipilimumab.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Anthony Olszanski, MD; Phone Number: 2152141676; Email: Anthony.Olszanski@fccc.edu
• Study Contact Backup: Name: Tanu Singh, PhD; Phone Number: 2152141439; Email: Tanu.Singh@fccc.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Anthony J. Olszanski; Phone Number: 215-214-1676; Email: Anthony.Olszanski@fccc.edu
      • Principal Investigator: Anthony J. Olszanski

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients must have:

   1. Pathologically proven stage III melanoma with one or more macroscopic lymph node metastases (measurable according to RECIST v. 1.1) amenable to biopsy and/or surgery OR:
   2. Patients considered to have stage III or stage IV disease amenable to serial biopsies as determined by the treating physician. Note: patients with in-transit metastasis may be eligible after surgical consultation if not surgical candidates.
   3. Patients must have disease amenable to and must be willing to undergo protocol-directed repeat biopsies and blood draws.
2. Age > 18 years
3. ECOG performance status 0 or 1
4. Patients must have normal organ and marrow function

Exclusion Criteria:

1. Patients may not be receiving any other investigational agents
2. Patients with a known active autoimmune disease
3. Prior treatment with CTLA-4 or PD1/PD-L1 pathway targeted systemic treatment
4. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic corticosteroids
5. Patients with ongoing diarrhea (> 4 bowel movements/day) unresolved despite medical and best supportive care in the two weeks preceding therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBL0137 (Dose level 1) +Ipilimumab + Nivolumab; Dose level 1 CBL0137 on Days 1 and 8, Nivolumab and Ipilimumab on days 8 and 29 administrated IV of 8 weeks treatment cycles.	Drug: CBL0137; Patient will be enrolled at 3 dose levels of CBL 0137, dose level -1 (320 mg/m²), dose level 1 (400 mg/m²), dose level 2 (540 mg/m²); Other Names: Curaxin; Drug: Ipilimumab; Patient will be on Ipilimumab (1 mg/kg); Drug: Nivolumab; Patient will be on Nivolumab (3 mg/kg)
Experimental: CBL0137 ( Dose level 2) +Ipilimumab + Nivolumab; Dose level 2 CBL0137 on Days 1 and 8, Nivolumab and Ipilimumab on days 8 and 29 administrated IV of 8 weeks treatment cycles.	Drug: CBL0137; Patient will be enrolled at 3 dose levels of CBL 0137, dose level -1 (320 mg/m²), dose level 1 (400 mg/m²), dose level 2 (540 mg/m²); Other Names: Curaxin; Drug: Ipilimumab; Patient will be on Ipilimumab (1 mg/kg); Drug: Nivolumab; Patient will be on Nivolumab (3 mg/kg)
Experimental: CBL0137 ( Dose level -1) +Ipilimumab + Nivolumab; Dose level -1 CBL0137 on Days 1 and 8, Nivolumab and Ipilimumab on days 8 and 29 administrated IV of 8 weeks treatment cycles.	Drug: CBL0137; Patient will be enrolled at 3 dose levels of CBL 0137, dose level -1 (320 mg/m²), dose level 1 (400 mg/m²), dose level 2 (540 mg/m²); Other Names: Curaxin; Drug: Ipilimumab; Patient will be on Ipilimumab (1 mg/kg); Drug: Nivolumab; Patient will be on Nivolumab (3 mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial assessment of safety and tolerability of the combination of CBL0137 with Nivolumab and Ipilimumab.	The primary endpoint will be safety/tolerability of the combination of CBL0137 with ipilimumab and nivolumab. Patients will be treated as part of assigned dose level in planned 3+ 3 design with 3 possible dose levels and assessed for Dose limiting toxicities ( DLTs)	28 days

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: Incuron
• Investigators: Principal Investigator: Anthony Olszanski, MD, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Estimated): March 4, 2027
• Study Completion (Estimated): September 2, 2027

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab; CBLC137
• Other Study ID Numbers: MEL-212; 22-1028 (Other Identifier: Fox Chase Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No