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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03684811




Registration number
NCT03684811
Ethics application status
Date submitted
17/09/2018
Date registered
26/09/2018
Date last updated
1/05/2019

Titles & IDs
Public title
A Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Scientific title
A Phase 1b/2 Study of FT 2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
Secondary ID [1] 0 0
2102-ONC-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cohort 1a and 1b: Glioma 0 0
Cohort 1a and 1b: Glioblastoma Multiforme 0 0
Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas) 0 0
Cohort 3a and 3b: Chondrosarcoma 0 0
Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma 0 0
Cohort 5a: Other Solid Tumors With IDH1 Mutations 0 0
Condition category
Condition code
Cancer 0 0 0 0
Liver
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FT-2102
Treatment: Drugs - Azacitidine
Other interventions - Nivolumab
Treatment: Drugs - Gemcitabine and Cisplatin

Experimental: Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a) -

Experimental: Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a) -

Experimental: Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b) -

Experimental: Phase 1b and 2 Cohort Combination (Cohort 2b) -

Experimental: Phase 1b and 2 Cohort Combination (Cohort 4b) -


Treatment: Drugs: FT-2102
FT-2102 will be supplied as 150 mg capsule and will be administered per the protocol defined frequency and dose level.

Treatment: Drugs: Azacitidine
Azacitidine will be administered per site's standard of care

Other interventions: Nivolumab
Nivolumab will be administered per site's standard of care

Treatment: Drugs: Gemcitabine and Cisplatin
Gemcitabine and Cisplatin will be administered per site's standard of care

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with a Dose Limiting Toxicity (DLT) [Phase 1]
Timepoint [1] 0 0
within first 4 weeks of treatment
Primary outcome [2] 0 0
Doses recommended for future studies [Phase 1]
Timepoint [2] 0 0
Participants to be followed for duration of participation, an expected average of 16 weeks
Primary outcome [3] 0 0
Objective response [CR+PR +MR (glioma only)] rate of FT-2102 single agent or in combination with azacitidine (glioma and chondrosarcoma), nivolumab (hepatobiliary tumors) and gemcitabine/cisplatin (intrahepatic cholangiocarcinoma) [Phase 2]
Timepoint [3] 0 0
within 4 months of treatment
Secondary outcome [1] 0 0
Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
Timepoint [1] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [2] 0 0
Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
Timepoint [2] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [3] 0 0
Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
Timepoint [3] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [4] 0 0
Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
Timepoint [4] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [5] 0 0
Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
Timepoint [5] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [6] 0 0
Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
Timepoint [6] 0 0
Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles (each cycle is 28 days) following the first 30 days
Secondary outcome [7] 0 0
Drug level within CSF (Glioma only) [Phase 1 and Phase 2]
Timepoint [7] 0 0
CSF sample for drug concentration collected at day 1 of cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average
Secondary outcome [8] 0 0
Overall response rate of FT-2102 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1]
Timepoint [8] 0 0
Response Assessment Guidelines for solid tumors or gliomas respectively and based on investigator's assessment within 4 months
Secondary outcome [9] 0 0
Incidence and severity of adverse events as assessed by CTCAE v4.0 as a single-agent or in combination with azacitidine or nivolumab or gemcitabine/cisplatin [Phase 1and 2]
Timepoint [9] 0 0
Safety will be assessed from time of first dose through 28 days post last dose
Secondary outcome [10] 0 0
Progression-Free Survival (PFS) [Phase 1b and 2]
Timepoint [10] 0 0
From time of entry on study through progression, up to 24 weeks, on average
Secondary outcome [11] 0 0
Time to Progression (TTP) [Phase 1b and 2]
Timepoint [11] 0 0
From first dose of study drug through time of first response by blood recovery count, up to 24 weeks, on average
Secondary outcome [12] 0 0
Duration of Response (DOR) [Phase 1b and 2]
Timepoint [12] 0 0
From time of first response by blood recovery count through relapse, up to 24 weeks, on average
Secondary outcome [13] 0 0
Overall Survival (OS) [Phase 1b and 2]
Timepoint [13] 0 0
From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average
Secondary outcome [14] 0 0
Time to Response (TTR) [Phase 1b and 2]
Timepoint [14] 0 0
From time of entry on study through death or date last known alive at end of follow-up, up to 24 weeks, on average

Eligibility
Key inclusion criteria
Key

- Patients must have documented IDH1-R132 gene-mutated disease as evaluated by site

- Glioma: Advanced glioma that has recurred or progressed following standard therapy, or
that has not responded to standard therapy.

- Hepatobiliary cancer that is relapsed/refractory or intolerant to approved
standard-of-care therapy (included: hepatocellular carcinoma, bile duct carcinoma,
intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)

- Chondrosarcoma that is relapsed or refractory and either locally advanced or
metastatic and not amenable to complete surgical excision

- Intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic
cholangiocarcinoma not eligible for curative resection or transplantation. Phase
1b/Safety Lead-in of Phase 2: relapsed or refractory disease. Combination Phase 2
(beyond Safety Lead-in): have received no more than 1 cycle of gemcitabine/cisplatin
therapy

- Other solid tumors that have relapsed or refractory to standard-of-care therapy with
no other available therapeutic options

- Good performance status

- Good kidney and liver function

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior solid organ or hematopoietic cell transplant

- Prior treatment with IDH1 inhibitor (Single agent cohorts only)

- Congestive heart failure (New York Heart Association Class III or IV) or unstable
angina pectoris. Previous history of myocardial infarction within 1 year prior to
study entry, uncontrolled hypertension or uncontrolled arrhythmias

- Unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function,
unstable pulmonary condition including pneumonitis and/or interstitial lung disease,
uncontrolled diabetes)

- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy

- PD-1 only: active autoimmune disease

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
VIC 3000 - Melbourne
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
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Forma Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single
agent and in combination with other anti-cancer drugs in patients with advanced solid tumors
and gliomas.

The study is divided into two parts: single agent FT-2102 followed by combination therapy.

Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors,
chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that
will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical
activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose
schedules may be explored.

Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients
will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 +
azacitidine (glioma and chondrosarcoma), FT-2102+nivolumab (hepatobiliary tumors) and
FT-2102+gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety
lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.
Trial website
https://clinicaltrials.gov/show/NCT03684811
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Blythe Thomson, MD
Address 0 0
Forma Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kathryn Lipford
Address 0 0
Country 0 0
Phone 0 0
857-209-2242
Fax 0 0
Email 0 0
klipford@formatherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03684811