A Multicenter Phase 1/2, Open-Label Study of DCC-3014 to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics in Patients with Advanced Tumors and Tenosynovial Giant Cell Tumor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deciphera Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 May 2020 → ongoing

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2024-514933-39-00

EudraCT number

2019-001856-21

ClinicalTrials.gov

NCT03069469

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenomic, Pharmacokinetic, Efficacy, Pharmacodynamic

- To assess the safety and tolerability of DCC-3014
- To characterize the pharmacokinetic (PK) profile of DCC-3014
- To determine the maximum tolerated dose (MTD) of DCC-3014
- To determine the recommended Phase 2 dose (RP2D) of DCC-3014
- To evaluate antitumor activity of DCC-3014 using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in tenosynovial giant cell tumor (TGCT; formerly known as pigmented villonodular synovitis [PVNS or giant cell tumor of the tendon sheath [GCT-TS]) (Expansion Cohort A only)

Secondary objectives 3

1. To evaluate antitumor activity of DCC-3014 using tumor volume score (TVS) and modified RECIST (mRECIST) (TGCT Expansion Cohort A only)
2. To assess the effects of DCC-3014 on range of motion (ROM) (TGCT Expansion Cohort A only)
3. To assess the effects of DCC-3014 on physical function, worst pain, and worst stiffness using patient reported outcome (PRO) measures (TGCT Expansion Cohort A only)

Conditions and MedDRA coding

Patients with Advanced Tumors and Tenosynovial Giant Cell Tumor

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male or female patients ≥18 years of age
2. Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis or giant cell tumor of the tendon sheath). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available at the time of screening
3. Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as determined by surgical consultation or a multidisciplinary tumor board
4. Symptomatic disease with at least moderate pain per BPI Worst Pain or at least moderate stiffness per Worst Stiffness numeric rating scale (NRS) item (defined as a score of 4 or more, with 10 describing the worst condition) within 30 days of the first dose documented in the medical record
5. Patient should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements outlined in Table 7
6. An analgesic regimen, if used, needs to be stable as judged by the Investigator for at least 2 weeks prior to Cycle 1 Day 1
7. Expansion Cohort B: prior systemic treatment with anti-CSF1 or antiCSF1R therapy, with the exception of imatinib or nilotinib
8. Patients must have at least 1 measurable lesion according to RECIST Version 1.1 (non-nodal lesions must be ≥1.0 cm in the long axis or ≥ double the slice thickness in the long axis; nodal lesions must be ≥1.5 cm in the short axis). A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion before study enrollment
9. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 21 days prior to the first dose of study drug: a. Bone marrow function: ANC ≥1500/μL; hemoglobin ≥10 g/dL; platelet count ≥lower level of normal b. Hepatic function: Total serum bilirubin ≤ULN; serum AST/ALT ≤ULN c. Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥ 50 mL/min based either on urine collection or Cockcroft-Gault estimation
10. Must be able to take oral medication
11. Patients of reproductive potential must: a. Have a negative serum β-hCG pregnancy test at screening for female patients, and b. Agree to follow the contraception requirements
12. The patient is capable of understanding and complying with the protocol and has signed the ICF. A signed ICF must be obtained before any study-specific procedures are performed
13. Must be willing and able to complete PRO assessments on an electronic device

Exclusion criteria 18

1. Expansion Cohort A: previous use of systemic therapy targeting CSF1 or CSF1R; previous therapy with imatinib and nilotinib is allowed
2. Expansion Cohort B: discontinuation of anti-CSF1 or anti-CSF1R due to drug-induced liver injury
3. Treatment with therapy for TGCT, including investigational therapy, within 14 days prior to the administration of study drug. For immediately prior therapies with a t1/2 longer than 3 days, or if the t1/2 is not available, the interval must be ≥28 days prior to the first administration of study drug
4. Known metastatic TGCT or other active cancer that requires concurrent treatment
5. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure
6. Systemic arterial thrombotic or embolic events, such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months prior to the start of study drug
7. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within the 1 month prior to the start of study drug
8. Baseline prolongation of QTcF based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome
9. LVEF <55%
10. Concurrent treatment with prohibited medications
11. Major surgery within 14 days of the first dose of study drug; following major surgeries >14 days prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence
12. Any clinically significant comorbidities, such as significant concomitant arthropathy in the affected joint, or any other serious medical or psychiatric condition(s), known current alcohol abuse, which in the judgment of the Investigator could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks
13. Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator
14. Known human immunodeficiency virus (HIV), active or chronic hepatitis B, active or chronic hepatitis C, or active mycobacterium tuberculosis infection
15. If female, the patient is pregnant or lactating
16. Known allergy or hypersensitivity to any component of the study drug
17. Contraindication to MRI
18. Active liver or biliary disease including evidence of fatty liver, nonalcoholic steatohepatitis (NASH), or cirrhosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Safety: DLTs, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose reduction or discontinuation of study drug due to toxicity, physical examination findings, ECOG PS, changes from baseline in laboratory parameters, electrocardiograms (ECGs), LVEF, and vital signs.
2. Pharmacokinetics: The following PK endpoints, including but not limited to, will be evaluated for both DCC-3014 parent and its metabolite, DP-7005, if detected: • Time to maximum observed concentration (Tmax) • Maximum observed concentration (Cmax) • Trough observed concentration (Cmin) • Area under the concentration-time curve (AUC) • t1/2
3. Efficacy (TGCT Expansion Cohort A only): • Objective response rate (ORR=complete response [CR]+partial response [PR]) assessed by independent radiological review using RECIST Version 1.1 at Week 25 (Cycle 7 Day 1) • Duration of Response (DOR; time from PR or CR to disease progression or death)

Secondary endpoints 4

1. ORR assessed by independent radiological review using TVS and mRECIST (TGCT Expansion Cohort A only)
2. ROM: change from baseline to Week 25 (Cycle 7 Day 1) (TGCT Expansion Cohort A only)
3. Response based on BPI worst pain NRS and narcotic analgesic use by Brief Pain Inventory-30 (BPI-30) at Week 25 (Cycle 7 Day 1) (TGCT Expansion Cohort A only)
4. PRO based upon the PROMIS physical function questionnaire and worst stiffness NRS: Change from starting value to Week 25 (Cycle 7 Day 1) (TGCT Expansion Cohort A only)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deciphera Pharmaceuticals Inc.

Sponsor organisation

Deciphera Pharmaceuticals Inc.

Address

200 Smith Street

City

Waltham

Postcode

02451-0099

Country

United States

Scientific contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Public contact point

Organisation

Deciphera Pharmaceuticals Inc.

Contact name

Clinical trial information

Third parties 14

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications