CD24Fc With Ipilimumab and Nivolumab to Decrease irAE (CINDI) (CINDI)

Phase Ib/II Study Combining CD24Fc With Checkpoint Inhibitors for Patients With Metastatic Melanoma

This is a phase Ib/II clinical trial to test safety and efficacy of combining CD24Fc with ipilimumab and nivolumab to decrease irAE, with built-in interim analyses, and safety and response stopping rules.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: CD24Fc; Drug: Ipilimumab; Drug: Nivolumab

Detailed Description

This is a phase 1b/II clinical trial using a fixed recommended phase 2 dose (RP2D) of CD24Fc to explore the safety and efficacy of combining CD24Fc with ipilimumab and nivolumab to reduce the toxicity of immunotherapy combination, in patients who are naïve to anti-PD1/L1 based checkpoint inhibitors. The dosing of nivolumab and ipilimumab will be fixed at FDA approved levels for each indication. Dosing of the drugs will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion is met. Patients who complete 12 months on study treatment and demonstrate clinical benefit with manageable toxicity will be given the opportunity to continue treatment for another 12 months upon agreement between investigator and drug manufacturers.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Male or female ≥18 years old.
2. Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a CD24Fc, anti-CTLA4 and anti-PD1/PDL1 inhibitors with documented progression.
3. Measurable disease per RECIST v1.1 criteria using imaging scans, or peripheral lesions that can be adequately documented with a picture and a ruler even if they do not meet RECIST criteria.
4. Patients must have lesion accessible for sequential biopsy (core needle biopsy or excision preferred, fine needle aspiration not eligible).
5. ECOG performance status 0 or 1.
6. Women of child-bearing potential must have a negative serum pregnancy test within 24 hour of initiation of dosing and must agree to use an effective form of contraception during the study from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Fertile men must also agree to use an effective method of birth control while on study drug and up to 6 months after the last dose of study drug.
7. Patients must have fully recovered from the effects of any major surgery or significant traumatic injury within 14 days of C1D1.

8. Adequate hematologic, hepatic, and renal function, as defined below:

   • Absolute neutrophil count ≥1 X 109/L,
   • Hgb > 8 g/dL
   • Platelet count ≥ 75 X 109/L,
   • AST/ALT/bilirubin ≤3X ULN (patients with Gilbert syndrome can have higher bilirubin levels).
   • Creatinine ≤ 3 X ULN or calculated CrCl > 30 mL/min using Cockcroft- Gault formula.
9. Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.

Exclusion Criteria

1. Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor.
2. Investigational drug use within 28 days of C1D1.
3. Chemotherapy, targeted therapy, growth factors or radiation therapy within 14 days of C1D1.
4. Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to C1D1.
5. Patients with known active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without clinical evidence of disease progression in the brain.
6. Has received a live vaccine within 28 days prior to C1D1.
7. A known active and clinically significant bacterial, fungal, or viral infection.
8. Active hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness, including patients who have an active infection requiring systemic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Advanced Melanoma; Patients with advanced melanoma.

Drug: CD24Fc; CD24Fc will be administrated as IV infusion in a dose of 480 mg, q3w x 4, then q4w for up to 6 times.; Other Names: Human CD24 and human IgG Fc Fusion Protein; Drug: Ipilimumab; Ipilimumab will be administrated as IV infusion, q3w x 4. For metastatic melanoma, the dose will be 3mg/kg, q3w x4.; Other Names: Yervoy, MDX-010.; Drug: Nivolumab; Nivolumab will be administrated as IV infusion. For metastatic melanoma, the dose will be 1mg/kg, q3w x 4, then 480 mg, q4w for up to 1 year.; Other Names: Opdivo, MDX-1106, BMS-936558

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of combination of CD24Fc with Ipilimumab and Nivolumab	The rate of Grade 3 or above treatment-related adverse events (TRAE) at 4 weeks after first dosing of drugs.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of treatment related adverse events	To tabulate the treatment related adverse events in 1 year	1 year
The Objective Response Rate (OPR)	The rate of objective response with CD24Fc, Ipilimumab, Nivolumab combination therapy at 1 year	1 year
The Progression Free Survival (PFS)	The rate of Progression Free Survival with CD24Fc, Ipilimumab, Nivolumab combination therapy at 1 year.	1 year
The Overall Survival (OS)	The rate of Overall Survival with CD24Fc, Ipilimumab, Nivolumab combination therapy at 1 year.	1 year

Collaborators and Investigators

• Sponsor: OncoImmune, Inc.
• Collaborators: National Cancer Institute (NCI); Huntsman Cancer Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2021
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: 7110-004; R44CA250889 (U.S. NIH Grant/Contract); CD24-004-CINDI (Other Identifier: OncoImmune)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No