A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)

NCT03668119 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CA209-8482016-002898-35
• Study Type: interventional
• Target: 212
• Locations: 17 countries
• Sites: 60

Brief Summary

The purpose of this study is to demonstrate the clinical activity of nivolumab in combination with ipilimumab in multiple types of tumors based on their Tumor Mutational Burden status.

Conditions

Pan Tumor

Keywords

TMB-H

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A

  ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment. RECIST Criteria: CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. RANO Criteria: CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.

  From date of randomization up to 42 months

Secondary Outcomes (13)

• Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm B

  From date of randomization up to 57 months

• Objective Response Rate (ORR) Per Investigator

  From date of randomization up to 57 months

• Duration of Response (DoR) Per Investigator

  From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

• Duration of Response (DoR) Per Blinded Independent Central Review (BICR)

  From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months)

• Time to Objective Response (TTR) Per Investigator

  From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months)

Study Arms (2)

Nivolumab + Ipilimumab Combination

EXPERIMENTAL

Biological: Nivolumab; Biological: Ipilimumab

Nivolumab Monotherapy

EXPERIMENTAL

Biological: Nivolumab

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Nivolumab + Ipilimumab Combination; Nivolumab Monotherapy

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: Yervoy, BMS-734016

Nivolumab + Ipilimumab Combination

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with high tumor mutational burden (TMB-H) who are refractory to standard local therapies, or for which no standard treatment is available.
• Must be able to provide tissue and blood TMB-H testing results
• Must have measurable disease for response assessment

You may not qualify if:

• Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease
• Participants who received prior treatment with an anti-programmed death-1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (60)

John Wayne Cancer Center

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Local Institution - 0093

Minneapolis, Minnesota, 55404, United States

Location

Broome Oncology

Johnson City, New York, 13790, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Local Institution - 0079

Portland, Oregon, 97239, United States

Location

Local Institution - 0095

Austin, Texas, 78731, United States

Location

Local Institution - 0094

Dallas, Texas, 75231, United States

Location

Local Institution - 0090

Houston, Texas, 77030, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Local Institution - 0016

Ciudad Autonoma Beunos Aires, Buenos Aires, 1431, Argentina

Location

Local Institution - 0087

Ciudad Autónoma de Buenos Aires, Buenos Aires, 1280, Argentina

Location

Local Institution - 0078

CABA, 1199, Argentina

Location

Local Institution - 0015

CABA, 1426, Argentina

Location

Local Institution - 0119

Córdoba, 5000, Argentina

Location

Local Institution - 0118

St Leonards, New South Wales, 2065, Australia

Location

Local Institution - 0062

Sydney, New South Wales, 2010, Australia

Location

Local Institution - 0117

Woolloongabba, Queensland, 4102, Australia

Location

Local Institution - 0112

Brussels, 1090, Belgium

Location

Local Institution - 0113

Brussels, 1200, Belgium

Location

Local Institution - 0114

Leuven, 3000, Belgium

Location

Local Institution - 0010

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 0060

Hamilton, Ontario, L8V 5C2, Canada

Location

Local Institution - 0036

Montreal, Quebec, H2X 3E4, Canada

Location

Local Institution - 0088

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 0018

Santiago, Santiago Metropolitan, 8330024, Chile

Location

Local Institution - 0082

Santiago, Santiago Metropolitan, 8420383, Chile

Location

Local Institution - 0080

Copenhagen, 2100, Denmark

Location

Local Institution - 0081

Herlev, 2730, Denmark

Location

Local Institution - 0072

Lyon, 69373, France

Location

Local Institution - 0075

Marseille, 13273, France

Location

Local Institution - 0073

Paris, 75248, France

Location

Local Institution - 0074

Toulouse, 31100, France

Location

Local Institution - 0085

Villejuif, 94805, France

Location

Local Institution - 0039

Berlin, 12200, Germany

Location

Local Institution - 0001

Bonn, 53127, Germany

Location

Local Institution - 0002

Dresden, 01307, Germany

Location

Local Institution - 0086

Essen, 45147, Germany

Location

Local Institution - 0043

Würzburg, 97080, Germany

Location

Local Institution - 0032

Genova, 16132, Italy

Location

IRCCS Istituto Nazionale Tumori Milano

Milan, 20133, Italy

Location

Local Institution - 0029

Napoli, 80131, Italy

Location

Local Institution - 0031

Siena, 53100, Italy

Location

Local Institution - 0116

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Local Institution - 0115

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0076

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Local Institution - 0077

Gdansk, 80-214, Poland

Location

Fundacion De Investigacion

San Juan, 00927, Puerto Rico

Location

Local Institution - 0068

Cluj-Napoca, Cluj, 400015, Romania

Location

Local Institution - 0069

Bucharest, 022328, Romania

Location

Local Institution - 0067

Craiova, 200542, Romania

Location

Local Institution - 0070

Floreşti, 407280, Romania

Location

Local Institution - 0071

Timisoara, Timis, 300239, Romania

Location

Local Institution - 0065

Singapore, Central Singapore, 168583, Singapore

Location

Local Institution - 0066

Singapore, 117599, Singapore

Location

Local Institution - 0084

Barcelona, 08035, Spain

Location

Local Institution - 0083

Madrid, 28041, Spain

Location

Local Institution - 0110

Pamplona, 31008, Spain

Location

Local Institution - 0106

London, Greater London, W12 OHS, United Kingdom

Location

Local Institution - 0107

Preston, PR2 9HT, United Kingdom

Location

Related Publications (1)

• Schenker M, Burotto M, Richardet M, Ciuleanu TE, Goncalves A, Steeghs N, Schoffski P, Ascierto PA, Maio M, Lugowska I, Lupinacci L, Leary A, Delord JP, Grasselli J, Tan DSP, Friedmann J, Vuky J, Tschaika M, Konduru S, Vemula SV, Slepetis R, Kollia G, Pacius M, Duong Q, Huang N, Doshi P, Baden J, Di Nicola M. Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden. J Immunother Cancer. 2024 Aug 6;12(8):e008872. doi: 10.1136/jitc-2024-008872.

  PMID: 39107131 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Interventions

Nivolumab; Ipilimumab

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: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 12, 2018
• Study Start: October 31, 2018
• Primary Completion: May 3, 2022
• Study Completion: August 2, 2023
• Last Updated: August 28, 2024
• Results First Posted: May 18, 2023

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); ES (3); US (10); NL (2); IT (4); PR (1); AU (3); DK (2); PL (2); DE (5); SG (2); RO (5); AR (5); BE (3); CA (4); CL (2); GB (2)