This is a multicenter, randomized, Phase 3 study with vimseltinib or placebo in patients with Tenosynovial Giant Cell Tumor, consisting of 2 parts: Part 1 is double blinded and Part 2 is open label study

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

16 Dec 2021 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2024-513624-42-00

EudraCT number

2020-004883-25

ClinicalTrials.gov

NCT05059262

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacogenomic, Pharmacokinetic

To evaluate anti-tumor activity of vimseltinib using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent radiological review (IRR)

Secondary objectives 4

1. To assess anti-tumor activity of vimseltinib using tumor volume score (TVS) and modified RECIST (mRECIST) by blinded IRR
2. To assess the effects of vimseltinib on range of motion (ROM)
3. To assess the effects of vimseltinib on physical function, worst stiffness, worst pain, and quality of life (QoL) using patient-reported outcome (PRO) measures
4. To assess safety and tolerability of vimseltinib

Conditions and MedDRA coding

Tenosynovial Giant Cell Tumor

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male or female participants ≥18 years of age
2. Histologically confirmed diagnosis of TGCT (formerly known as pigmented villonodular synovitis [PVNS] or giant cell tumor of the tendon sheath [GCT-TS]). Tumor biopsy to confirm TGCT diagnosis will be required if no histology/pathology is available. a. Participants should have TGCT in a single joint and must have TGCT in joints where ROM can be assessed
3. Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity as judged by surgical consultation or a multidisciplinary tumor board
4. Symptomatic disease with at least moderate pain or at least moderate stiffness (defined as a score of 4 or more, with 10 describing the worst condition) within the screening period and documented in the medical record
5. Participant should complete 14 consecutive days of questionnaires during the screening period and must meet minimum requirements outlined in Protocol Table 4
6. An analgesic regimen, if used, needs to be stable( ie, no change in dose) as judged by the Investigator for at least 2 weeks prior to the first dose of study drug
7. Measurable disease per RECIST v1.1 with at least one lesion having a minimum size of 2 cm as assessed from magnetic resonance imaging (MRI) scans by a central radiologist
8. 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: absolute neutrophil count (ANC) ≥1500/μL; hemoglobin ≥10 g/dL; platelet count ≥lower limit of normal (LLN). b. Hepatic function: total serum bilirubin ≤upper limit of normal (ULN); serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ULN. c. Renal function: creatinine clearance ≥50 mL/min based either on urine collection or Cockcroft-Gault estimation. d. Electrolytes ≥LLN for: potassium, magnesium, and calcium
9. Able to take oral medication
10. Participants of reproductive potential must: a. Have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening (female participants). b. Agree to follow the contraception requirements outlined in the protocol
11. The participant is capable of understanding and complying with the protocol and has signed the informed consent form (ICF). A signed ICF must be obtained before any study-specific procedures are performed.
12. Willing and able to complete the PRO assessments on an electronic device

Exclusion criteria 13

1. Previous use of systemic therapy (investigational or approved) targeting CSF1 or CSF1R including vimseltinib; previous therapy with imatinib and nilotinib is allowed
2. Treatment for TGCT, including investigational therapy, during the screening period. NOTE: Participants may not be part of an ongoing or have prior participation in a non TGCT investigational drug study within 30 days of screening. Ongoing participation in a noninterventional study (including observational studies) is permitted
3. Known metastatic TGCT or other active cancer that requires concurrent treatment (exceptions will be considered on a case-by-case basis depending on tumor type, stage, location, planned treatment, and expected recovery after discussion and approval by Sponsor)
4. Baseline prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females or history of long QT syndrome
5. Receive concurrent treatment with any prohibited medications • Acetaminophen usage exceeding 3 g/day • Proton-pump inhibitors taken within 4 days prior to the first dose of study drug • Medications that are breast cancer resistance protein (BCRP) or organic cation transporter 2 (OCT2) substrates taken within at least 4 days or 5×half-life (whichever is longer) prior to the first dose of study drug • Medications with a known risk of prolonging the QT interval within at least 14 days or 5×half-life (whichever is longer) prior to the first dose of study drug (see Appendix 1) • Prophylactic use of myeloid growth factors (eg, granulocyte colonystimulating factor [G-CSF], granulocyte macrophage-colony-stimulating factor [GM-CSF])
6. 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
7. Any clinically significant comorbidities, such as significant concomitant arthropathy not related to TGCT 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 participant to safety risks
8. Active liver or biliary disease including non-alcoholic steatohepatitis (NASH), or cirrhosis
9. Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator
10. Known active human immunodeficiency virus (HIV), acute or chronic hepatitis B, acute or chronic hepatitis C, or known active mycobacterium tuberculosis infection
11. If female, the participant is pregnant or breastfeeding
12. Known allergy or hypersensitivity to any component of the study drug
13. Contraindication to MRI

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR, including complete response [CR] and partial response [PR]) per RECIST v1.1 at Week 25

Secondary endpoints 11

1. ORR per TVS at Week 25
2. Change from baseline in active ROM of the affected joint, relative to a reference standard, at Week 25
3. Change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) physical function score at Week 25
4. Change from baseline in the Worst Stiffness numeric rating scale (NRS) score at Week 25
5. Change from baseline in EQ-VAS (EuroQol Visual Analogue Scale) at Week 25
6. Response of at least a 30% improvement in the mean Brief Pain Inventory (BPI) Worst Pain NRS score without a 30% or greater increase in narcotic analgesic use at Week 25
7. ORR per RECIST v1.1
8. ORR assessed by mRECIST at Week 25
9. Duration of response (DOR; time from first PR or CR to disease progression or death) assessed using RECIST v1.1, TVS, and mRECIST
10. Incidence of treatment-emergent adverse events (TEAEs), treatmentemergent serious adverse events, related TEAEs, dose reductions, dose interruptions, and discontinuation of study drug due to adverse event
11. Changes from baseline in laboratory parameters, electrocardiograms (ECGs), and vital signs

Investigational products

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

Test 2

Placebo 1

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 15

Locations

7 EU/EEA countries · 14 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 87 files

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

Application history

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