John Bridgewater, MD, Ph.D. @uclcancer #livercancer Phase 2 Study FOENIX-CCA2 and Efficacy and Safety of Futibatinib

John Bridgewater, MD, Ph.D. @uclcancer #livercancer Phase 2 Study FOENIX-CCA2 and Efficacy and Safety of Futibatinib

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John Bridgewater, MD, Ph.D., Medical Oncologist discusses ESMO abstracts Efficacy and Safety of Futibatinib in Intrahepatic Cholangiocarcinoma (iCCA) Harboring FGFR2 Fusions/Other Rearrangements: Subgroup Analyses of a Phase 2 Study (FOENIX-CCA2) and Quality of Life Outcomes With Futibatinib Treatment in FOENIX-CCA2, a Phase 2 Study in Patients With Intrahepatic Cholangiocarcinoma Harboring FGFR2 Gene Fusions/Rearrangements.


1 - Efficacy and Safety of Futibatinib in Intrahepatic Cholangiocarcinoma (iCCA) Harboring FGFR2 Fusions/Other Rearrangements: Subgroup Analyses of a Phase 2 Study (FOENIX-CCA2)

Context
FGFR2 fusions occur with iCCA and tumor suppressor computations in 10-20 percent of pts.  There may be prognostic genes. An analysis of futibatinib (highly selective) is FOENIX-CCA2.   An irreversible inhibitor of FGFR1–4) with iCCA and FGFR2 fusions / other rearrangements in pts.

Methodology
Locally advanced/metastatic iCCA with FGFR2 fusions / other pts enrolled is
Progressive disease (PD) rearrangements after ~1 systemic therapy (tx), no prior FGFR
Inhibitor tx, and PS 0/1 ECOG. Oral futibatinib 20 mg 1x / day was administered to Pts before intolerance / PD. The primary Objective Response Rate (ORR; independent review) was the secondary endpoints were endpoint and period of response (DOR), PFS, and protection. Subanalyses were performed by pt function, fusion, computation, and prognostic factor.

Outcomes
Interim data is recorded for 67 pts (58 percent female; median age 57 y) with ⁇ 6 mo of follow-up. Pts had fusions (82%) or rearrangements (18%) of FGFR2. FGFR2-BICC1 (n=15) was the most common fusion. ORR was 37.3 percent, median DOR 8.3 mo, and 82 percent of the disease control average. ORR was 36.2 percent (21/58 fusions) and 44.4 percent (4/9 rearrangements) in pts with confirmed FGFR2 modifications. With FGFR2-BICC1, ORR was 33.3 percent in pts. The best overall answer in pts with interest calculations is shown (table). There were responding pts for all baseline characteristic subgroups (e.g., age, gender, prior tx), including pts aged 65 y (ORR= 57 percent; 8/14). In responders vs. nonresponders, higher phosphate levels trended. Treatment of grade x3-   at a median of 6 d, the associated hyperphosphatemia was resolved. Control of AEs of specific interest would be added.

Findings
These interim data demonstrate manageable AEs and futibatinib efficacy in iCCA with futibatinib fusions of FGFR2 / other rearrangements. Responses were observed across subgroups of pt, including those with common fusions of FGFR2, calculations, and weak prognostic variables.

2 - Quality of Life Outcomes With Futibatinib Treatment in FOENIX-CCA2, a Phase 2 Study in Patients With Intrahepatic Cholangiocarcinoma Harboring FGFR2 Gene Fusions/Rearrangements

Context
Futibatinib Clinical Experience
Futibatinib is a new, highly selective, active, and irreversible small-molecule inhibitor of all 4 isoforms of the fibroblast growth factor receptor (FGFR),1.2
In the Phase 1 dose-escalation trial, futibatinib 20 mg once daily (QD) was defined as the maximum tolerated dose and the recommended treatment schedule3
Objective responses to futibatinib have been identified in the phase 1 dose-escalation / expansion analysis in patients with different advanced tumor forms (including cholangiocarcinoma, urothelial carcinoma, breast cancer, and gastric cancer) with a spectrum of FGFR alterations3,4
In an interim review of the phase 2 FOENIX-CCA2 (NCT02052778) trial of patients with advanced/refractory intrahepatic cholangiocarcinoma (iCCA) containing FGFR2 fusions/rearrangements (see ESMO poster # 54P), Futibatinib demonstrated objective and durable responses and a tolerable and manageable safety profile (Table 1).
Quality of life assessment in the FOENIX-CCA2 phase 2 analysis (81 percent), diarrhea (37 percent), and dry mouth (33 percent)
Optimal symptom control is a crucial factor in enhancing the quality of life of patients (QoL) during cancer treatment,5 however there is a lack of awareness of how iCCA therapies impact patient QoL6.
A planned evaluation of patient-reported outcomes (PROs) related to patient QoL was conducted in phase 2 FOENIX-CCA2 study to evaluate the following:-change in health-related QoL from baseline through 13 futibatinib treatment cycles-whether health-related QoL deteriorates throughout therapy
Health-related QoL data from the interim review of the FOENIX-CCA2 study are recorded here for patients with 6 months of follow-up.
The shift from baseline in PRO measures mean global health status scores for QLQ-C30 were retained for 273 days, from baseline (68.7; n=57) through cycle 13 (70.8; n=20) through cycle 13. Changes in QLQ-C30 scores from baseline to cycle 13 were stable across individual functional and symptom scales. For constipation (which worsened at cycles 2 and 4) and dyspnea, a MID of about 10 points was observed. FOENIX-CCA22 (which changed in cycle 10)

Project Research
Overall, constipation symptoms resolved over a period of 141 days in 16 out of 27 patients.
Mean EQ-5D-3L VAS scores improved from 70.9 at baseline (n=56) to 79.1 at Patient Care Endpoints Follow-up ddp (suggested improvement) The 13th cycle (n=19).

Main Conditions of Eligibility
Unresectable iCCA or metastatic
• Main: primary:
FGFR2 fusions or other (centrally confirmed) rearrangements
Panel 1. Table 1. Protection of Futibatinib in iCCA patients
Safety population (N=67), n (percent)a Grade 3b TRAEs of any grade 67 (100) 38 (57) Most popular (preferred term) TRAEs
Hyperphosphatemia 54 (81) 18 (27) Diarrhea 25 (37) 0 Dry mouth 22 (33) 0 Severe TRAEs 7 (10) Research drug changes due to TRAEs 44 (66) Drug interruption 37 (55) Drug dose reduction 34 (51) Drug withdrawal 1 (1) Death-related TRAEs 0 AE, adverse event; iCCA, cholangiocarcinoma intrahepatic; TRAE, adverse event associated with medication. Between the first dose and 30 days after the last dose of the study drug, the aAEs were registered. Patients with ~2 AEs are counted once in every group. There were no Grade 4 or 5 TRAEs recorded. Oh. Table 2. Completion Rates PRO QuestionnairePatients with a completed examination, n (percent)aa
Timepoint of completed evaluation QLQ-C30 EQ-5D-3L All patients (N=67) Baseline 57 (85) 57 (85) PRO population (n=57) Baseline plus ⁇ 1 additional time point 50 (88) 51 (89) EORTC, European Organization for Cancer Research and Treatment; EQ-5D-3L, EuroQol-Five 3-Level Instrument Dimensions; PRO, patient-reported result.

Objective rate of response (by ICR)
• Observable illness according to RECIST v1.1.1.
Secondary •:
• Previous chemotherapy based on gemcitabine + platinum
Progression following systematic therapy of ~1
Answer duration (key)-Rate of disease control-Progression-free
Survival of ECOG PS 0 or 1
• No previous FGFR inhibitor therapy
Maximum 2 dose reductions (up to 16 mg and then up to 12 mg) have been authorized for treatment management-emergent AEsc

Findings
Such PRO data is the first to be recorded in the iCCA patient population for a FGFR inhibitor.
For most functional and symptom measurements, QLQ-C30 scores (QoL measure) were stable from baseline through cycle 13 without any clinically relevant changes.
Mean EQ-5D-3L VAS (general health status measure) scores showed an growing pattern from baseline to cycle 13, suggesting an increase in the health of these patients.
86 percent of patients retained an ECOG PS of 0 or 1, while 57 percent of patients encountered a grade 3 TRAE in the interim study, indicating that TRAEs were manageable.
Overall, PRO data from the FOENIX-CCA2 interim population indicated that treatment with futibatinib did not negatively affect patient QoL, and overall health status showed a trend towards change.
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