87.5% ORR | Abbisko presented two clinical updates of Pimicotinib at the 2023 CTOS Annual Meeting

SHANGHAI, Nov. 6, 2023 /PRNewswire/ — Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics” hereafter) announced that two major clinical updates of its CSF-1R inhibitor pimicotinib（ABSK021）were presented at the 2023 Connective Tissue Oncology Society Annual Meeting, which is held in Ireland from November 1 to 4, 2023. The two clinical updates include reporting the design of the pivotal global multi-center phase III clinical trial and the further update of the phase Ib clinical trial of pimicotinib.

A sustained improvement has been observed relative to the 6-month data earlier reported in CTOS last year of pimicotinib, with an Objective Response Rate (ORR) of 87.5% (28/32, including 3 Complete Response) in 50 mg quaque die (QD) cohort and 66.7% (8/12, including 2  Complete Response) in 25 mg quaque die (QD) cohort by Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1).

Abbisko presented the following posters at the CTOS:

Abstract number: 1572315

Title：Updated efficacy and safety profile of Pimicotinib (ABSK021) in tenosynovial giant cell tumor (TGCT): 1-year follow-up from phase 1b

Objective: TGCT is a rare class of locally aggressive neoplasm, predominantly driven by overexpression of colony-stimulating factor 1 (CSF-1) gene. Pimicotinib, an orally administered selective small-molecule antagonist of CSF-1R, exhibits minimal inhibition of c-Kit and PDGFR. In 2023, the U.S. FDA conferred Breakthrough Therapy Designation and the European Medicines Agency granted Priority Medicine Designation upon Pimicotinib treatment of TGCT. Here, we report the phase 1b safety and efficacy results of Pimicotinib in TGCT patients over a 1-year follow-up.

Methods：The study (NCT04192344) entailed a TGCT cohort to evaluate the safety and preliminary antitumor activity of Pimicotinib in TGCT patients not amenable to surgical resection. The study investigated two dosage regimens: 50 mg once daily (QD) and 25 mg QD.

Results:

1. Clinical characteristics of patients

As of 31 May 2023, a total of 56 TGCT patients were enrolled, comprising 44 patients in the 50 mg QD and 12 patients in the 25 mg QD cohort. Median age was 39 y (range: 18-76) and 41.1% were male. Tumors were primarily located in knee (48.2%), hip (16.1%) or ankle (10.7%). Prior to enrollment, thirty-two patients (57.1%) had undergone at least one tumor resection surgery.

2. Efficacy Data

A sustained improvement has been observed relative to the 6-month data earlier reported in CTOS last year, with an ORR of 87.5% (28/32, including 3 CR) in 50 mg QD cohort and 66.7% (8/12, including 2 CR) in 25 mg QD cohort by IRC based on RECIST 1.1 (RES). Out of the 16 patients who achieved a PR within the first 6 mos and had follow-up data available, 15 of them (93.8%) sustained this response beyond 6 mos. Out of 5 patients who achieved SD within the first 6 mos and had follow-up data, 4 (80%) patients improved to PR after 6 mos. Median DOR was not reached in either cohort. Durable improvements in range of motion, stiffness and pain over a 1-year follow-up were observed in both dose cohorts.

3. Safety Data

Extended follow-up indicated that Pimicotinib was well-tolerated, with a median treatment duration of 12.2 mos and the maximum treatment duration being 17.5 mos. 83.9% patients remained on treatment. The majority of TEAEs were Grade 1 to 2. Most common drug-related TEAEs (≥15%) include LDH increase (80.4%), CPK increase (67.9%), α-HBDH increase (62.5%), AST increase (42.9%), amylase increase (30.4%), ALT increase (25.0%), pruritus (21.4%), rash (19.6%), face oedema (19.6%) and dyslipidaemia (19.6%). No hair color change or serious liver injuries were reported, meanwhile, blood enzymes elevations were asymptomatic, within the expected range, and quickly recovered following drug interruptions, all of which were consistent with previous observations. Compared to the data within 6 mos, the overall safety profile remains largely consistent with no distinct adverse events emerging upon extended follow-up.

Conclusion: Pimicotinib has demonstrated significant anti-tumor efficacy and good safety profile. With the extension of treatment duration, there is an observed augmentation in the number of patients experiencing sustained tumor shrinkage and favorable safety of Pimicotinib with no apparent hepatotoxicity. Current data confers durable therapeutic benefits in TGCT patients, suggesting that prolonged exposure may represent an optimal treatment approach. In addition, a separate cohort with prior anti-CSF-1/CSF-1R therapies is underway to assess the safety and antitumor activity.

Abstract number: 1572315

Title： MANEUVER Study: A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study of Pimicotinib (ABSK021) to Assess the Efficacy and Safety in Patients with Tenosynovial Giant Cell Tumor

Objective

TGCT is a rare type of locally aggressive neoplasm that is primarily caused by overexpression of colony-stimulating factor 1 (CSF1) gene. Pimicotinib is an oral, highly potent, and selective small-molecule antagonist of CSF-1R with minimum inhibition of c-Kit and PDGFR. In a Phase 1b study, Pimicotinib demonstrated significant antitumor activity with the ORR of 77.4% in 50 mg QD cohort by IRC based on RECIST1.1, and a favorable safety profile with no apparent hepatotoxicity (Xu et al, ASCO 2023) in TGCT patients. No apparent ethnic differences were observed for PK and PD data among different ethnic groups based on data from Phase 1 study. Pimicotinib has been granted Breakthrough Therapy Designation (BTD) by China NMPA and US FDA, and PRIority MEdicines (PRIME) Designation by the European Medicines Agency for treating TGCT. MANEUVER study (NCT05804045) is a Phase 3, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of ABSK021 at the dose of 50 mg QD in patients with unresectable TGCT. The study marks the first global Phase 3 trial assessing a CSF-1R inhibitor in TGCT patients across Asia, North America and Europe.

Study Design

MANEUVER study consists of two parts. Part 1 is a double-blind phase, approximately 90 eligible patients will be randomized in a 2:1 ratio to 50mg QD ABSK021 treatment group or matching placebo group and will receive consecutive treatment until the completion of Part 1. The randomization will be stratified by geographical location, China vs. non-China sites. All patients who complete Part 1 and meet eligibility criteria will proceed to Part 2. In Part 2, open-label treatment phase, all patients entering this phase will receive open-label 50 mg QD of ABSK021 until the completion of 24 weeks of dosing or withdrawal from the study. Patients who complete 24 weeks of dosing in Part 2 may be eligible for extended treatment.

Study Endpoints

The primary endpoint is 25-week ORR by Blinded Independent Review Committee (BIRC) based on RECIST 1.1. Key secondary endpoints comprise 25-week ORR by BIRC based on Tumor Volume Score, the mean change from baseline in Range of Motion of the affected joint at week 25, the mean change from baseline in the Worst Stiffness and Worst Pain NRS score at week 25, and the mean change from baseline in the PROMIS Physical Functioning score at week 25.

Study Population

Key inclusion criteria include patients that are, histologically confirmed TGCT and not amenable to surgical resection, existing measurable disease, willingness and ability to complete PRO assessments, symptomatic disease (based on level of pain and stiffness), and age of 18 or older. Key exclusion criteria include previous treatment with highly selective inhibitors targeting CSF-1/CSF-1R (Imatinib and Nilotinib are allowed), known metastatic TGCT or MRI contraindications, major surgery or previous anti-tumor therapy within 4 weeks prior to randomization. An Independent Data Monitoring Committee (IDMC) will be established to continuously monitor the safety profile and oversee the overall conduct of the study.

Results: Enrollment is ongoing, approximately 40 sites around the world will participate in this study.

Conclusion: Not applicable

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SOURCE Abbisko