Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

• ClinicalTrials.gov Identifier: NCT03773302
• Recruitment Status: Terminated
• First Posted: December 12, 2018
• Last Update Posted: April 3, 2023
• Sponsor: QED Therapeutics, Inc.
• Collaborator: Helsinn Healthcare SA
• Information provided by (Responsible Party): QED Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 10, 2018
• First Posted Date: December 12, 2018
• Last Update Posted Date: April 3, 2023
• Actual Study Start Date: December 27, 2019
• Actual Primary Completion Date: March 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2020)

Progression-free survival (central imaging assessment) [ Time Frame: Approximately 11 months on average ]

Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors [RECIST] v. 1.1) or death, whichever occurs first.

Original Primary Outcome Measures (submitted: December 10, 2018)

Number of participants with progression-free survival (Central Imaging Assessment) [ Time Frame: Month 12 ]

Defined as the time from randomization until date of disease progression by central independent imaging assessment (Response Evaluation Criteria in Solid Tumors [RECIST] v. 1.1) or death, whichever occurs first.

Current Secondary Outcome Measures (submitted: January 17, 2020)

• Overall survival in participants treated with infigratinib versus gemcitabine with cisplatin [ Time Frame: Approximately 15 months on average ]
  Defined as time from date of randomization until death due to any cause
• Investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin [ Time Frame: Approximately 10 months on average ]
  Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
• Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by overall response rate (ORR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
• Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by best overall response (BOR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
• Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by duration of response (DOR) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
• Evaluate the efficacy in participants treated with infigratinib versus gemcitabine with cisplatin by disease control rate (PR+CR+SD) determined by blinded independent central assessment and the investigator. [ Time Frame: Approximately 10 months on average ]
• Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability of infigratinib. [ Time Frame: Approximately from baseline to last dose date of study treatment + 30 days, approximately 12 months on average ]

Original Secondary Outcome Measures (submitted: December 10, 2018)

• Percentage of overall survival in participants treated with infigratinib versus gemcitabine with cisplatin [ Time Frame: Month 12 ]
  Defined as time from date of randomization until death due to any cause
• Percentage of investigator assessed progression free survival in participants treated with infigratinib compared to gemcitabine and cisplatin [ Time Frame: Month 12 ]
  Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
• Official Title: A Phase 3 Multicenter, Open-Label, Randomized, Controlled Study of Oral Infigratinib Versus Gemcitabine With Cisplatin in Subjects With Advanced/Metastatic or Inoperable Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations: The PROOF Trial
• Brief Summary: Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Advanced Cholangiocarcinoma
• FGFR2 Gene Mutation

Intervention

• Drug: BGJ398
  Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
  Other Name: Infigratinib
• Drug: Gemcitabine
  Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.
• Drug: Cisplatin
  Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Study Arms

• Experimental: Infigratinib (BGJ398) 125 mg
  Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
  Intervention: Drug: BGJ398
• Active Comparator: Gemcitabine + Cisplatin
  Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.
  Interventions:

  • Drug: Gemcitabine
  • Drug: Cisplatin

• Publications *: Makawita S, K Abou-Alfa G, Roychowdhury S, Sadeghi S, Borbath I, Goyal L, Cohn A, Lamarca A, Oh DY, Macarulla T, T Shroff R, Howland M, Li A, Cho T, Pande A, Javle M. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 29, 2023): 48
• Original Estimated Enrollment (submitted: December 10, 2018): 350
• Actual Study Completion Date: March 1, 2023
• Actual Primary Completion Date: March 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
• Have written documentation of local laboratory or central laboratory determination of a known or likely activating FGFR2 fusion/rearrangement from a sample collected before randomization
• Have an archival tumor tissue sample available with sufficient tumor content for FGFR2 fusion/rearrangement molecular testing by the central laboratory. However, if an archival tumor tissue sample is not available, or does not meet requirements for central testing a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Are able to swallow and retain oral medication
• Are willingness to avoid pregnancy or father children

Exclusion Criteria:

• Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions

  1. Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant therapy.
  2. One cycle of gemcitabine-based chemotherapy for locally advanced or metastatic cholangiocarcinoma is permitted before randomization
• History of a liver transplant
• Received previously or currently is receiving treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor
• Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
• Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
• History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
• Current evidence of corneal or retinal disorder/keratopathy
• Receiving and continued treatment or are planning to receive agents or consuming foods that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration
• Clinically significant or uncontrolled cardiac disease
• Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
• Severe hearing loss
• Severe neuropathy
• History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment
• Pregnant or breastfeeding
• Have known microsatellite instability-high (MSI-H) disease and the decision is made by the treating investigator that an alternative, non-study therapy is warranted according to standard of care.
• Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients
• Have any contraindication to cisplatin or gemcitabine treatment according to local labeling or standard institutional practice.
• Have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
• Have received a live vaccine within 30 days before the first dose of study drug or are planning to receive a live vaccine during participation in this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, China, France, Germany, Italy, Korea, Republic of, Portugal, Puerto Rico, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT03773302
• Other Study ID Numbers: QBGJ398-301; 2018-004004-19 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: QED Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: QED Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Helsinn Healthcare SA

Investigators

• Study Director: Clinical Development; QED Therapeutics

• PRS Account: QED Therapeutics, Inc.
• Verification Date: March 2023