Avadomide (CC-122) in Combination With Nivolumab in Advanced Melanoma

A Phase II Biomarker Trial of Avadomide (CC-122) in Combination With Nivolumab in Advanced Melanoma

This study is to find out if the combination of CC-122 (an investigational agent) and Nivolumab will enhance the anti-cancer activity and prevent T-cell exhaustion (T-cells are responsible for maintaining the body's immune response).

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: CC-122; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research 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:

• Unresectable or metastatic melanoma of cutaneous, mucosal, conjunctival, or unknown origin. Uveal melanoma is not permitted. Cohort 1: Naïve to anti-PD1 therapy Cohort 2: Progressed on previous anti-PD1 therapy. Subjects who have received anti-PD1 therapy in the adjuvant setting for previously resected melanoma are eligible for this cohort provided they have not received any intervening systemic therapy for the relapse
• Be willing and able to provide written informed consent for the trial.
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Females of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
• Females of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study 28 days after last dose of avadomide or 5 months after the last dose of nivolumab, whichever is longer. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
• Males should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of avadomide or 7 months after last dose of nivolumab, whichever is longer.
• Adequate organ function

Exclusion Criteria:

• Has received an investigational drug or other anti-cancer therapy within 3 weeks of the first dose of treatment or < 5 half-lives of that agent, whichever is shorter. Any toxicity from prior therapy must have recovered to < grade 1.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (only exception to this is the need for steroids for CNS metastases; see #6 below). Inhaled, intra-articular, or topical steroids are permissible.
• Has a history of hypersensitivity to nivolumab.
• Has a known additional malignancy that is progressing or requires active treatment, the lack of which would pose a risk to the health of the subject, in the opinion of the investigator.
• Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging for at least four weeks after definitive intervention and using no more than the equivalent of dexamethasone 2mg/d for the management of vasogenic edema, if necessary. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy [</= 10 mg/d equivalent of prednisone] for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with previous grade III/IV toxicity from immunotherapy that led to treatment discontinuation are excluded.
• Has an active infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the investigator.
• Is pregnant or breastfeeding.
• Has a known history of Human Immunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C.
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed

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: CC-122 Plus Nivolumab; Participants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.	Drug: CC-122; Oral CC-122 at 2 mg daily, 5 days out of 7; Other Names: Avadomide; Drug: Nivolumab; 240 mg Nivolumab intravenously days 1 and 15 in each 28 day cycle; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate of CC-122 in Combination With Nivolumab	Objective Response Rate of CC-122 in combination with Nivolumab in both anti-PD1 therapy naive advanced melanoma as well as anti-PD1 therapy refractory melanoma (primary refractory or progressing after an initial response or stable disease)	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience Treatment Related Adverse Events	All Adverse Events and Serious Adverse events will be collected and collated according to grade and frequency. This will include all events considered possibly, probably or definitely related to study therapy.	Up to 52 weeks
Tumor Response	Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and and iRECIST (Response Evaluation Criteria in Solid Tumors in immunotherapy) guidelines v1.1. Results will be indicated as number of participants with evaluable tumor response.	Up to 52 weeks
Progression Free Survival	Progression free survival will be calculated from the start of study therapy till the first documentation of disease progression, death, or change of treatment. Subjects receiving ongoing therapy at the time of data analysis will be censored	Up to 24 months
Overall Survival	Overall survival will be calculated from the start of therapy till death from any cause. Subjects alive at the time of data analysis will be censored.	Up to 24 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Bristol-Myers Squibb; Celgene Corporation
• Investigators: Principal Investigator: Nikhil Khushalani, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2019
• Primary Completion (Actual): June 29, 2021
• Study Completion (Actual): August 4, 2021

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: skin; melanoma
• 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
• Other Study ID Numbers: MCC-19706

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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