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

Phase 3TerminatedNCT03773302

QED Therapeutics, a BridgeBio company48 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Cholangiocarcinoma FGFR2 Gene Mutation

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (116)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

University of Arizona

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

St. Joseph Heritage Healthcare

Fullerton, California, United States

USC Norris Cancer Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

Progression-free Survival (Central Imaging Assessment)

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.

Time frame: From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.

Secondary Outcomes

Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin

OS by investigator assessment, defined as time from date of randomization until death due to any cause

Time frame: From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive.

Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin

Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.

Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment

ORR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR) or confirmed complete response (CR) as assessed by BICR and the investigator according to RECIST v1.1 among patients with measurable disease at baseline

Time frame: From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).

Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator.

BOR was defined as the best response a subject ever achieved after study treatment prior to crossover and any subsequent anticancer therapy, complete response (CR) and partial response (PR) were claimed only if the criteria for each were met at a subsequent time point at least 4 weeks apart. In the case of stable disease (SD), measurements must have met the SD criteria at least once post-baseline no less than 6 weeks from the randomization date.

Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator.

DOR is defined as the time from initiation of confirmed partial response (PR) or confirmed complete response (CR) to the time of confirmed progressive disease (PD) or death. If subjects do not reach PD or death before crossover, the DOR is censored at the last valid tumor assessment before crossover.

Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator.

DCR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR), confirmed complete response (CR) or stable disease (SD) or non-CR/non-PD before crossover.

Number of Participants With Adverse Events (AEs)

Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period

Time frame: From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).

Number of Participants With Serious Adverse Events (SAEs)

Time frame: From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).