Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy

NCT02731729 | Completed Phase 2 Results

• 2 other identifiers: PICI000116-043
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this research study is to learn whether patients whose disease grows after being treated with nivolumab or pembrolizumab respond to ipilimumab (Yervoy®) alone or in combination with nivolumab (Opdivo®).

Conditions

Melanoma

Keywords

Ipilimumab; Nivolumab; Stage III-IV Melanoma; Progressed or Relapsed on PD-1 Inhibitor Therapy; 16-043

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) as Defined by RECIST v1.1 at Week 18

  Overall Response Rate was defined as any participant who had a Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1 by week 18 of treatment.

  Week 18

Secondary Outcomes (5)

• Disease Control Rate (DCR) Status at Week 18

  Week 18

• Time to Treatment Failure (TTF)

  The time from treatment initiation until a subsequent therapy is started or death.

• Overall Survival (OS)

  Death

• Number of Participants With Grade 3 or 4 Adverse Events

  AE were monitored during each treatment cycle and could be reported until 30 days after the last dose of study treatment had been administered.

• Disease Control Rate (DCR) Status at Week 12

  Week 12

Study Arms (2)

ipilimumab and nivolumab

EXPERIMENTAL

For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes.

Drug: ipilimumab; Drug: nivolumab

ipilimumab

EXPERIMENTAL

In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses.

Drug: ipilimumab

Interventions

ipilimumab DRUG

Also known as: Yervoy

ipilimumab; ipilimumab and nivolumab

nivolumab DRUG

Also known as: Opdivo

ipilimumab and nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Joint Committee on Cancer (AJCC) (2009) Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Patients with a history of uveal melanoma are not eligible.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with computerized tomography (CT) scan. Patients must have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) and a separate lesion amenable to biopsy.
• Histologic proof of melanoma reviewed and confirmed by the enrolling site.
• Previous treatment with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with documented progression of disease on most recent CT scan. Progression of disease is defined as 1) the appearance of a new measureable lesion (\>10 mm) on cross-sectional imaging or physical examination OR 2) enlargement of previously detected lesions on two consecutive imaging studies OR 3) enlargement of a previously detected lesion with correlative symptomatology on one cross-sectional imaging study. Patients remain eligible if they had a previous response to a PD-1 inhibitor, including patients who had a complete response, partial response or stable disease (SD). Primary progressing patients are defined as those who received anti-PD-1 therapy within 2 months of study enrollment. Patients with relapsed disease are defined as those who received their last dose of PD-1 blocking antibody ≥2 months prior to enrollment.
• Patients who received adjuvant PD-1 therapy who then develop measurable disease are eligible. However, they must have received their last dose of PD-1/PD-L1 blockade within two months of enrollment in this study. They will be stratified with patients who have primary progressive disease.
• Life expectancy of greater than 3 months.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group performance status = 0 or 1 or Karnofsky Performance Status equivalent.
• Patients must have adequate organ and marrow function as defined below:
• White blood cells \>2, 000/microliter (mcL)
• Absolute neutrophil count \>1,500/mcL
• Platelets \>100,000/mcL
• Hemoglobin \> 9.0 g/dL
• Total bilirubin ≤ 1.5 X institution's upper limit of normal
• Aspartate aminotransferase (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X institution's upper limit of normal for patients with no concurrent liver metastases, OR ≤ 5 X institution's upper limit of normal for patients with concurrent liver metastases

You may not qualify if:

• History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible. Consult the study Medical Monitor if unsure whether second malignancies meet the requirements specified above.
• Any major surgical procedures or external beam radiotherapy within 14 days prior to study drug administration.
• Use of other investigational drugs within 28 days prior to study drug administration.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month and require treatment with less than 10mg/day prednisone equivalent for at least 2 weeks prior to study drug administration.
• Prior exposure to either ipilimumab or combined checkpoint blockade.
• Any diagnosis of autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, adrenal insufficiency on replacement dose steroids, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Pregnant women and lactating women.
• History of uveal melanoma.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV or HCV infection, which will be allowed). Once-documented negative result for HIV, HBV, and HCV is sufficient.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted.
• Patients with history of any grade 4 toxicity during previous anti PD-1 treatment or history of Grade 3 or higher pneumonitis.
• Patients with a history of Grade ≥2 neuropathy.
• Prisoners or patients who are involuntarily incarcerated.
• Children under the age of 18.

Sponsors & Collaborators

• Parker Institute for Cancer Immunotherapy: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94134, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Friedman CF, Spencer C, Cabanski CR, Panageas KS, Wells DK, Ribas A, Tawbi H, Tsai K, Postow M, Shoushtari A, Chapman P, Karakunnel J, Bucktrout S, Gherardini P, Hollmann TJ, Chen RO, Callahan M, LaVallee T, Ibrahim R, Wolchok J. Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses. J Immunother Cancer. 2022 Jan;10(1):e003853. doi: 10.1136/jitc-2021-003853.

  PMID: 35074903 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Ute Dugan
• Organization: Parker Institute for Cancer Immunotherapy

udugan@parkerici.org

203-379-6757

Study Officials

• Ramy Ibrahim, MD

  Parker Institute for Cancer Immunotherapy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2016
• First Posted: April 7, 2016
• Study Start: June 21, 2016
• Primary Completion: August 27, 2018
• Study Completion: February 13, 2019
• Last Updated: December 23, 2022
• Results First Posted: February 21, 2021

Record last verified: 2022-12

Locations

US (7)