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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04370704




Registration number
NCT04370704
Ethics application status
Date submitted
29/04/2020
Date registered
1/05/2020

Titles & IDs
Public title
Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies
Scientific title
A Phase 1-2 Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies
Secondary ID [1] 0 0
INCAGN 2385-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INCAGN02385
Treatment: Drugs - INCAGN02390
Treatment: Drugs - INCMGA00012.

Experimental: Phase 1 Part 1 - Part 1 will confirm the safety of INCAGN02385 and INCAGN02390 when used in combination. INCAGN02385 will be administered first intravenously followed by INCAGN02390.

Experimental: Phase 1 Part 2 - Part 2 will confirm the safety of the triple combination of INCAGN02385 + INCAGN02390 + INCMGA00012, following confirmation of the safety of the doublet in Part 1. INCAGN02385 will be administered first intravenously followed by INCAGN02390 and INCMGA00012.

Experimental: Phase 2 Cohort A - Phase 2 will determine preliminary efficacy and proof of concept for the combination of INCAGN02385 + INCAGN02390 + INCMGA00012. INCAGN02385 will be administered first intravenously followed by INCAGN02390 and INCMGA00012

Experimental: Phase 2 Cohort B - Phase 2 will determine preliminary efficacy and proof of concept for the combination of INCAGN02385 + INCAGN02390 + INCMGA00012. INCAGN02385 will be administered first intravenously followed by INCAGN02390 and INCMGA00012

Experimental: Phase 1 Part 3 - Part 1 will confirm the safety of INCAGN02385 + INCAGN02390 + INCMGA00012 when used in combination.

Experimental: Phase 1 Part 4 - Part 1 will confirm the safety of INCAGN02385 + INCAGN02390 + INCMGA00012 in combination.


Treatment: Drugs: INCAGN02385
INCAGN02385 administered intravenously

Treatment: Drugs: INCAGN02390
INCAGN02390 administered intravenously

Treatment: Drugs: INCMGA00012.
INCMGA00012 administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phases 1 & 2: Participants with treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
28 days after end of study approximately 24 months
Primary outcome [2] 0 0
Phase 2 Cohort A and B: Objective Response Rate (ORR)
Timepoint [2] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months
Primary outcome [3] 0 0
Phase 2 Cohort A and B: Duration of Response (DOR)
Timepoint [3] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months
Primary outcome [4] 0 0
Phase 2 Cohort A and B: Disease Control Rate (DCR)
Timepoint [4] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months
Primary outcome [5] 0 0
Phase 2 Cohort A and B: Progression-free Survival (PFS)
Timepoint [5] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months
Secondary outcome [1] 0 0
Phase 1 : Objective Response Rate
Timepoint [1] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months
Secondary outcome [2] 0 0
Phase 1 : Progression Free Survival
Timepoint [2] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months
Secondary outcome [3] 0 0
Phase 1: Disease Control Rate (DCR)
Timepoint [3] 0 0
Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

Eligibility
Key inclusion criteria
* Phase 1 Parts 1-4): Participants with locally advanced or metastatic solid tumors (locally advanced disease must not be amenable to resection with curative intent) that have failed available therapies, including anti-PD-(L)1 therapy if applicable, that are known to confer clinical benefit, or who are intolerant to, or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.
* Phase 2, Cohort A:

1. Participant with histologically confirmed unresectable/metastatic melanoma, whose disease failed prior anti-PD-(L)1 therapy (alone or as part of a combination) and meeting one of the following criteria:

* Participant who failed prior adjuvant anti-PD-(L)1 therapy for resectable melanoma must have received prior anti-PD-(L)1 for = 6 weeks and experienced disease progression while still on active adjuvant therapy containing anti-PD-(L)1, or participant who had early relapse occurring < 24 weeks after end of adjuvant anti-PD-(L)1 therapy. Progressive disease must be ascertained by confirmatory biopsy collected at baseline.
* Participant whose unresectable/metastatic disease progressed while on or within < 24 weeks of completion of anti-PD-(L)1 for inresectable/metastatic melanoma. Progressive disease must have been confirmed by imaging = 4 weeks after evidence of initial disease progression.
2. Participant must have received no more than 2 prior lines of therapy for melanoma and at least one prior regimen must have contained anti-PD-(L)1 therapy (alone or as part of a combination) either in the adjuvant and/or advanced/metastatic setting.
3. Participants must have had known BRAF V600 mutation status per local institutional testing standards.
4. Participants must have fresh biopsy available after completing prior PD-(L)1 therapy or be willing and able to safely undergo pretreatment tumor biopsies (core or excisional). Determination of whether participants can safely undergo biopsy should be made by the treating physician in consultation with the individual performing the biopsy.
5. Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
* Phase 2, Cohort B:

1. Participant with previously untreated, histologically confirmed Stage III (unresectable) or IV melanoma per the American Joint Committee on Cancer v8 staging system.
2. Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma.
3. Participants must have had known BRAF V600 mutation status per local institutional testing standards.
4. Participants must have fresh biopsy available or be willing and able to safely undergo pretreatment tumor biopsies (core or excisional). Determination of whether participants can safely undergo biopsy should be made by the treating physician in consultation with the individual performing the biopsy.
* Phase 2 (Cohorts A and B): Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
* ECOG performance status 0 or 1.
* Willingness to avoid pregnancy or fathering children
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 outside the protocol-defined range.
* Known hypersensitivity or severe reaction to any component of the study drugs or formulation components ) within 14 days before study Day 1.
* Participant who had prior treatment with a LAG-3 or TIM-3 targeted agent.

Phase 1: (Parts 1-4):

* Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study treatment:

1. =28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.
2. Administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
* Phase 2:
* Cohort A: Participant who has discontinued anti-PD-(L)1 therapy due to toxicity or other reasons unrelated to toxicity, then subsequently experienced disease progression.
* Cohort A: Participant who had experienced objective response (PR/CR) and had stopped anti-PD-(L)1 therapy due to maximal benefit.
* Cohort A: Participant with multiple metastases that achieved mixed tumor response to prior anti-PD-(L)1 therapy (such as isolated progressive lesion in a context of PR/CR or SD for other lesions) or achieved overall disease progression based only on a single new lesion.
* Cohort B: Participant who has or has had uveal melanoma.
* Receipt of anticancer therapy (immunotherapy, chemotherapy, targeted therapy or hormonal therapy) within 21 days of the first administration of study treatment, with the exception of localized radiotherapy.
* Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment.
* If participant received major surgery, then they must have recovered adequately from toxicities and/or complications from the intervention before starting study treatment.
* Treatment-related toxicity related to prior therapy that has not recovered to = Grade 1 (with the exception of alopecia and anemia not requiring transfusional support), unless approved by the medical monitor.
* History of immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy is recommended (per product label or consensus guidelines), OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well controlled on stable dose of replacement hormones such as hypothyroidism or adrenal insufficiency, or Grade 3 rashes that resolved with topical therapy or asymptomatic lipase elevations that do not require treatment interruption or uveitis that resolved with steroid drops).
* Has an active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 14 days before the first dose of study treatment.
* Receiving chronic systemic corticosteroids (> 10 mg/day of prednisone or equivalent).
* Active infections requiring systemic antibiotics, or antifungal or antiviral treatment within 7 days before first dose of study treatment.
* History of organ transplant, including allogeneic stem cell transplantation.
* Evidence of interstitial lung disease or active, noninfectious pneumonitis.
* Known active HBV or HCV infection or risk of reactivation of HBV or HCV.
* Participants who are known to be HIV-positive .
* Known active brain or CNS metastases including carcinomatous meningitis.
* Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy after treatment with curative intent.
* Participants with impaired cardiac function or clinically significant cardiac disease
* History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
* Women who are pregnant or breastfeeding.
* Receipt of a live vaccine within 30 days of planned start of study treatment.

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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/08/2025
Actual
Sample size
Target
Accrual to date
Final
61
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment hospital [2] 0 0
Greenslopes Private Hospital - Brisbane
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
One Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
02060 - Wollstonecraft
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
05042 - Bedford Park
Recruitment postcode(s) [4] 0 0
03128 - Box Hill
Recruitment postcode(s) [5] 0 0
06009 - Nedlands
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
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Incyte Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
Available to whom?
Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.incyte.com/our-company/compliance-and-transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04370704