Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03126110




Registration number
NCT03126110
Ethics application status
Date submitted
19/04/2017
Date registered
24/04/2017
Date last updated
28/12/2022

Titles & IDs
Public title
Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies
Scientific title
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies
Secondary ID [1] 0 0
INCAGN 1876-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Malignancies 0 0
Metastatic Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INCAGN01876
Treatment: Drugs - Nivolumab
Treatment: Drugs - Ipilimumab

Experimental: Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W - Participants received INCAGN01876 1.0 milligrams per kilogram (mg/kg) administered intravenously (IV) every 2 weeks (Q2W) in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W - Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W - Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W - Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then nivolumab 240 mg Q2W - Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Experimental: Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then nivolumab 240 mg Q2W - Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Experimental: Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, then nivolumab 240 mg Q2W - Participants received INCAGN01876 5.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 5.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Experimental: Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W - Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W).

Experimental: Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W - Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Experimental: Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W - Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Experimental: Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab - Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with nivolumab 3 mg/kg administered IV Q2W and ipilimumab 1 mg/kg administered IV Q6W.

Experimental: Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg - Participants with programmed cell death protein/programmed cell death ligand 1 (PD-1/PD-L1) relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Experimental: Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg - Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg - Participants with squamous cell carcinoma of the head and neck (SCCHN) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg - Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg - Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Experimental: Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg - Participants with gastric cancer, squamous cell carcinoma of the head and neck, cervical cancer, or PD-1/PD-L1 relapsed melanoma who had tumor lesions that were amenable to percutaneous biopsy received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.


Treatment: Drugs: INCAGN01876
In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Treatment: Drugs: Nivolumab
Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Treatment: Drugs: Ipilimumab
Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Timepoint [1] 0 0
up to approximately 27.4 months
Primary outcome [2] 0 0
Phase 2: Objective Response Rate (ORR) Per RECIST v1.1
Timepoint [2] 0 0
up to approximately 44.7 months
Secondary outcome [1] 0 0
Phase 1: ORR Per RECIST v1.1
Timepoint [1] 0 0
up to approximately 44.7 months
Secondary outcome [2] 0 0
Phase 1: ORR Per Modified RECIST (mRECIST) v1.1
Timepoint [2] 0 0
up to approximately 44.7 months
Secondary outcome [3] 0 0
Phase 2: ORR Per mRECIST v1.1
Timepoint [3] 0 0
up to approximately 44.7 months
Secondary outcome [4] 0 0
Phase 1: Duration of Response (DOR) Per RECIST v1.1
Timepoint [4] 0 0
up to approximately 44.7 months
Secondary outcome [5] 0 0
Phase 2: DOR Per RECIST v1.1
Timepoint [5] 0 0
up to approximately 44.7 months
Secondary outcome [6] 0 0
Phase 1: DOR Per mRECIST v1.1
Timepoint [6] 0 0
up to approximately 44.7 months
Secondary outcome [7] 0 0
Phase 2: DOR Per mRECIST v1.1
Timepoint [7] 0 0
up to approximately 44.7 months
Secondary outcome [8] 0 0
Phase 1: Disease Control Rate (DCR) Per RECIST v1.1
Timepoint [8] 0 0
up to approximately 44.7 months
Secondary outcome [9] 0 0
Phase 2: DCR Per RECIST v1.1
Timepoint [9] 0 0
up to approximately 44.7 months
Secondary outcome [10] 0 0
Phase 1: DCR Per mRECIST v1.1
Timepoint [10] 0 0
up to approximately 44.7 months
Secondary outcome [11] 0 0
Phase 2: DCR Per mRECIST v1.1
Timepoint [11] 0 0
up to approximately 44.7 months
Secondary outcome [12] 0 0
Phase 1: Duration of Disease Control Per RECIST v1.1
Timepoint [12] 0 0
up to approximately 44.7 months
Secondary outcome [13] 0 0
Phase 2: Duration of Disease Control Per RECIST v1.1
Timepoint [13] 0 0
up to approximately 44.7 months
Secondary outcome [14] 0 0
Phase 1: Duration of Disease Control Per mRECIST v1.1
Timepoint [14] 0 0
up to approximately 44.7 months
Secondary outcome [15] 0 0
Phase 2: Duration of Disease Control Per mRECIST v1.1
Timepoint [15] 0 0
up to approximately 44.7 months
Secondary outcome [16] 0 0
Phase 1: Progression-free Survival (PFS) Per RECIST v1.1
Timepoint [16] 0 0
up to approximately 44.7 months
Secondary outcome [17] 0 0
Phase 2: PFS Per RECIST v1.1
Timepoint [17] 0 0
up to approximately 44.7 months
Secondary outcome [18] 0 0
Phase 1: PFS Per mRECIST v1.1
Timepoint [18] 0 0
up to approximately 44.7 months
Secondary outcome [19] 0 0
Phase 2: PFS Per mRECIST v1.1
Timepoint [19] 0 0
up to approximately 44.7 months
Secondary outcome [20] 0 0
Phase 1: Overall Survival
Timepoint [20] 0 0
up to approximately 44.7 months
Secondary outcome [21] 0 0
Phase 2: Overall Survival
Timepoint [21] 0 0
up to approximately 44.7 months
Secondary outcome [22] 0 0
Phase 2: : Number of Participants With Any TEAE
Timepoint [22] 0 0
up to approximately 27.4 months

Eligibility
Key inclusion criteria
- Locally advanced or metastatic disease; locally advanced disease must not be amenable
to resection with curative intent.

- Phase 1: Subjects with advanced or metastatic solid tumors.

- Phase 1: Subjects who have disease progression after treatment with available
therapies.

- Phase 2: Subjects with advanced or metastatic cervical cancer, gastric cancer
(including stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN and PD-1/PD-L1
relapsed melanoma.

- Presence of measurable disease based on RECIST v1.1.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Laboratory and medical history parameters not within the Protocol-defined range

- Prior treatment with any tumor necrosis factor super family agonist.

- Receipt of anticancer medications or investigational drugs within protocol-defined
intervals before the first administration of study drug.

- Has not recovered to = Grade 1 from toxic effects of prior therapy.

- Active autoimmune disease.

- Known active central nervous system metastases and/or carcinomatous meningitis.

- Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.

- Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

- Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/11/2021
Sample size
Target
Accrual to date
Final
145
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Scientia Clinical Research - Randwick
Recruitment hospital [3] 0 0
Greenslopes Private Hospital - Brisbane
Recruitment hospital [4] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [5] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2148 - Randwick
Recruitment postcode(s) [3] 0 0
4120 - Brisbane
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Belgium
State/province [14] 0 0
Chevigny
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerpen
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles
Country [18] 0 0
Belgium
State/province [18] 0 0
Charleroi
Country [19] 0 0
Belgium
State/province [19] 0 0
Ghent
Country [20] 0 0
Belgium
State/province [20] 0 0
Kortrijk
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Córdoba
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pamplona
Country [25] 0 0
Spain
State/province [25] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Incyte Biosciences International Sàrl
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety, tolerability, and efficacy of
INCAGN01876 when given in combination with immune therapies in subjects with advanced or
metastatic malignancies.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03126110
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John E. Janik, MD
Address 0 0
Incyte Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03126110