A Phase 2 Study Evaluating Futibatinib (TAS-120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic bladder, urethra or pelvis cancer

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

7 Sep 2021 → 17 Sep 2025

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513760-26-00

EudraCT number

2020-000945-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy

To evaluate the objective response rate (ORR) of futibatinib in
combination with pembrolizumab in patients with advanced or
metastatic UC who are not candidates to receive a platinum-based
treatment regimen.

Secondary objectives 2

1. •To assess the safety of futibatinib in combination with pembrolizumab.
2. •To evaluate the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Conditions and MedDRA coding

Advanced or Metastatic Urothelial Carcinoma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Histologically confirmed advanced or metastatic UC in patients who have not received systemic treatment for advanced metastatic disease. For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. a. In safety lead-in: enrollment regardless of FGFR status b. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement c. Cohort B: all other patients with UC (including patients with other FGFR or nonFGFR genetic aberrations and patients with WT [nonmutated] tumors)
2. 2. Unfit for or intolerant to cisplatin as defined by any one of the following criteria: a. Chronic kidney disease characterized by the estimated creatinine clearance rate (eCCr) per Cockcroft-Gault formula of <60 mL/min or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 , corresponding to NCI-CTCAE v.5.0 Grade ≥2 b. Impaired hearing (measured by audiometry) of >25 dB at two contiguous test frequencies in at least one ear, corresponding to NCI-CTCAE v.5.0 Grade ≥2 c. Peripheral sensory neuropathy Grade ≥2 by NCI-CTCAE v.5.0. Please refer to protocol for addition inclusion criteria.
3. 3. Be willing and able to provide written informed consent for the trial.
4. 4. Be ≥18 years of age.
5. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
6. 6. Adequate organ function as defined by the following criteria: a. Absolute neutrophil count (ANC) ≥1.5 × 109 /L b. Platelet count ≥100,000/mm3 c. Hemoglobin ≥9.0 g/dL d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤5.0 × ULN. e. Total bilirubin ≤1.5 × ULN, or ≤3.0 × ULN for patients with Gilbert's syndrome. f. Creatinine clearance (Ccr) (calculated or measured value): ≥30 mL/min. For calculated Ccr, use the Cockcroft-Gault formula. g. International normalized ratio (INR) OR prothrombin time ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as prothrombin time or aPTT is within therapeutic range of intended use of anticoagulants h. Phosphorus <1.5 ULN
7. 7. Adequate recovery from the side effects of any prior therapy for nonmetastatic disease (generally defined as recovery of all AEs due to ≤ Grade 1 or baseline; however, patients with ≤ Grade 2 neuropathy, anemia, alopecia, and skin pigmentation may be eligible).
8. 8. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
9. 9. Have a measurable disease per RECIST 1.1, as assessed by the local site Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
10. 10. A male patient must agree to use contraception during the treatment period and for at least 6 months following the last dose of study treatment.
11. 11. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP). b. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment. c. A WOCBP who has a negative serum pregnancy test within 7 days prior to treatment.
12. 12. Ability to take medications orally (feeding tube is not permitted).
13. 13. Willing and able to comply with scheduled visits and study procedures.

Exclusion criteria 17

1. 1. Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent.
2. 10. 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 is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
3. 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
4. 12. Have known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, that is, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without steroid treatment requirement for at least 1 month prior to the first dose of study treatment.
5. 13. The patient is pregnant or breastfeeding.
6. 14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
7. 15. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
8. Criteria 16 and for Protected Persons, see Protocol Addendum 2, dated 3 May 2021 section 4.2 and 4.2.1
9. 2. Have received prior FGFR inhibitor treatment including futibatinib
10. 3. History and/or current evidence of any of the following disorders: a. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator b. Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator c. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
11. 4. Corrected QT interval using Fridericia's formula (QTcF) >470 msec. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply.
12. 5. Has received major surgery within the previous 4 weeks.
13. 6. Has received any non-investigational anticancer therapy within the previous 3 weeks (mitomycin within the previous 5 weeks).
14. 7. Is currently participating in a study of an investigational agent/device, or has participated in a study of an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment.
15. 8. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
16. 9. A serious illness or medical condition(s) including, but not limited to, the following: a. Has an active infection requiring systemic therapy. b. Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months c. History or current evidence of uncontrolled ventricular arrhythmia d. Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator e. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death f. Have 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. g. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. h. Have had an allogenic tissue/ organ transplant.
17. Please refer to protocol for addition exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR), defined as the proportion of patients experiencing a best overall response of complete response (CR) or partial response (PR).

Secondary endpoints 5

1. -Disease control rate (DCR), defined as the proportion of patients experiencing a best overall response of stable disease (SD), PR, or CR.
2. ·Duration of response (DOR), defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.
3. ·Progression-free survival (PFS), defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression, whichever occurs first.
4. ·Overall survival (OS), defined as the time from the date of the first dose to the death date.
5. ·Safety and tolerability, based on reported adverse events (AEs) and on-study laboratory parameters, graded according to the National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Taiho Oncology Inc.

Sponsor organisation

Taiho Oncology Inc.

Address

101 Carnegie Center Suite 101

City

Princeton

Postcode

08540-6231

Country

United States

Scientific contact point

Organisation

Taiho Oncology Inc.

Contact name

Medical Monitor

Public contact point

Organisation

Taiho Oncology Inc.

Contact name

Medical Monitor

Third parties 5

Locations

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

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

Application history

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