Phase 2 Futibatinib in Combination with PD-1 Antibody-based Standard of Care in Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Taiho Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 May 2024 → ongoing

Decision date (initial)

2024-03-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Taiho Oncology Inc.

External identifiers

EU CT number

2023-507516-12-00

ClinicalTrials.gov

NCT05945823

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Pharmacodynamic, Pharmacokinetic

To evaluate the antitumor efficacy of futibatinib in combination with PD-1 antibody and standard of care chemospherapy.

Secondary objectives 2

1. To evaluate safety and tolerability
2. To evaluate further efficacy parameters

Conditions and MedDRA coding

Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Provide written informed consent prior to any study-specific procedures and are willing to comply with all study procedures
2. Women of child-bearing potential (WOCBP) must have a negative pregnancy test. Female patients are not considered to be of child-bearing potential if they are permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or are post-menopausal (no menses for 12 months without an alternative medical cause)
3. Willing and able to comply with scheduled visits and study procedures
4. Is ≥18 years of age at the time of informed consent (or meets the country’s regulatory definition for legal adult age)
5. Histologically or cytologically confirmed, locally advanced, unresectable or metastatic carcinoma: a. Cohort A: Adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ). b. Cohort B: Pancreatic ductal adenocarcinoma.
6. No prior systemic treatment for locally advanced, unresectable or metastatic EC (esophageal carcinoma) or PDAC (pancreatic ductal adenocarcinoma).
7. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009). A lesion(s) situated in a previously irradiated area can be considered a target lesion(s) if progression has been demonstrated and the lesion(s) is considered measurable per RECIST 1.1 criteria
8. ave documentation of PD-L1 CPS score (Cohort A only).
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
10. Have adequate organ function as exemplified in the protocol
11. Able to take medications orally
12. Cohort B only: Has archival tumor tissue available for submission to the central laboratory.

Exclusion criteria 23

1. Has locally advanced esophageal carcinoma or pancreatic cancer that is resectable or potentially curable with radiation therapy (as determined by local investigator)
2. Has an esophageal carcinoma or pancreatic cancer that is known to be eligible to receive approved targeted therapy (eg, HER-2 positive patients dMMR/MSI-high, germline BRCAmt).
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
4. Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C antibody or RNA. Active Hepatitis C virus (HCV) is defined by a known positive Hepatitis C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (that is, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
6. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
7. Has had an allogenic tissue/organ transplant
8. Is unable to swallow tablets/capsules or has any disease or condition that may significantly affect gastrointestinal absorption of futibatinib (eg, inflammatory bowel disease, malabsorption syndrome, or prior gastric/bowel resection)
9. Is judged by the investigator to be ineligible as a participant of the clinical study
10. Has known hypersensitivity or severe reaction to any of the study drugs or their excipients, including severe reaction to fluoropyrimidine therapy.
11. Has received prior treatment with an anti-PD-1/PD-L1 or FGF/FGFR targeting drug, or any other agent directed to stimulatory or co-stimulatory T-cell receptor
12. Has known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen. Exceptions must be discussed with the Sponsor prior to patient enrollment
13. Has had treatment as defined in the protocol within the specified time frame prior to the first dose of study treatment
14. Has a serious illness or medical condition(s)
15. Has a history or current evidence of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (except commonly observed calcifications in soft tissues such as the skin, kidney, tendons, or vessels due to injury, disease, and aging in the absence of systemic mineral imbalance)
16. Has current evidence of clinically significant retinal disorder as confirmed by ophthalmological examination
17. Is pregnant or lactating female
18. Have a complete absence of dihydropyrimidine dehydrogenase (DPD) activity (blood uracil level ≥150ng/ml).
19. Has some safety specific values defined in the protocol for patients selected to receive oxaliplatin.
20. Has some specific symptoms defined in the protocol for patients selected to receive cisplatin
21. Patients who have a persistent Grade ≥2 toxicity related to prior treatment.
22. Exclusion only applicable for France
23. Exclusion only applicable for Germany

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by investigator assessment

Secondary endpoints 5

1. Safety based on AEs, SAEs, dose modifications, clinical laboratory parameters, vital signs, electrocardiograms (ECGs), and ophthalmological exams
2. Duration of response (DoR) by investigator assessment
3. Disease control rate (DCR) by investigator assessment
4. Progression-free survival (PFS) by investigator assessment
5. 6-month PFS rate by investigator assessment

Investigational products

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

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Taiho Oncology Inc.

Sponsor organisation

Taiho Oncology Inc.

Address

101 Carnegie Center Suite 300

City

Princeton

Postcode

08540-6231

Country

United States

Scientific contact point

Organisation

Taiho Oncology Inc.

Contact name

Hamdy Elsayed

Public contact point

Organisation

Taiho Oncology Inc.

Contact name

Hamdy Elsayed

Third parties 6

Locations

3 EU/EEA countries · 6 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 24 files

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

Application history

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