58MO - Evaluation of three pexidartinib doses in a global phase IV clinical study of patients with tenosynovial giant cell tumor (TGCT) who chose to continue treatment

Background

In 2019, pexidartinib was US FDA-approsssved (800 mg/day TDD) for TGCT patients with severe morbidity or functional limitations not amenable to improvement with surgery. Per label, dose modifications are recommended in certain scenarios, yet long-term data at dosages <800 mg/day are lacking. We evaluated efficacy and safety of 3 doses in a phase 4 study designed to evaluate pexidartinib discontinuation/rechallenge in patients with TGCT.

Methods

This multicenter, open-label, nonrandomized study (NCT04526704) enrolled adults with TGCT from 4 prior pexidartinib trials (NCT02371369; NCT01004861; NCT02734433; NCT03291288). After the prior trials’ end-of-treatment (EOT) visits, patients could choose to enter the Treatment Continuation Cohort (TCC; same dose as EOT) or Treatment-Free/Re-Treatment Cohort (TF/RTC; discontinue pexidartinib with choice to re-initiate at the investigator’s/patient’s discretion). This secondary analysis studied the proportion of progressive disease (PD) by investigator-assessed RECIST v1.1 and safety of 3 pexidartinib doses (800 mg, 600 mg, 400 mg) utilized in the TCC.

Results

From Oct 2020-Apr 2021, 32 patients enrolled; 21/32 chose the TCC with a median age of 47 (range: 21-78) years, 57% (12/21) were female, and 48% (10/21) had knee tumors. In the TCC, 10 (48%), 6 (29%) and 5 (24%) patients were treated at daily doses of 800 mg, 600 mg, and 400 mg, respectively. Patient characteristics were well-balanced across dose, with a median of 10.8 (range: 4.6-32.6) years since diagnosis and a median of 55.3 (range: 26.7-91.0) months of historical pexidartinib treatment. Four of the 21 patients (19%) discontinued this study early due to AE (n = 1; 800 mg), patient withdrawal (n = 2; 800 mg), or physician decision (n = 1; 400 mg). In an average 22.4±4.4 months of follow-up, no TCC patients showed RECIST PD. 19 TCC patients (10 [100%], 6 [100%], 3 [60%] on 800 mg, 600 mg, and 400 mg, respectively) had TEAEs.

Conclusions

Patients who continued pexidartinib experienced disease control with a manageable safety profile across 3 doses. Further evaluation of long-term pexidartinib activity following dose modification is warranted.

Clinical trial identification

NCT04526704; EudraCT 2020-000192-20.

Editorial acknowledgement

Editorial assistance was provided by Heather Nyce, PhD, of Lumanity Scientific Inc., and was financially supported by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

S. Stacchiotti: Financial Interests, Personal, Advisory Role: Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Ikena, Maxivax, Novartis, PharmaMar, RainThera, and Servier; and institutional and financial interests from Advenchen, Bayer, Bo. A.J. Wagner: Financial Interests, Personal, Other, Consultant: Aadi Bioscience, BioAtla, Boehringer Ingelheim, Cogent Biosciences, Daiichi Sankyo, Deciphera, Eli Lilly, InhibRx, Kymera, and Servier; Financial Interests, Personal, Research Grant: Aadi Bioscience, Cogent Biosciences, Daiichi Sankyo, Deciphera, Eli Lilly, Foghorn, Karyopharm Therapeutics, Plexxikon, and Rain Therapeutics. I.C. Carrasco Garcia: Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Other, Consulting, and travel expenses: PharmaMar. C. Lin: Financial Interests, Personal, Advisory Role: AbbVie, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Merck KGaA, Novartis, and PharmaEngine; received honorarium from Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novartis and Roche; Financial Interests, Personal, Other, Travel: BeiGene, Daiichi Sankyo, Eli Lilly, and IMPACT Therapeutics.. C.W. Ryan: Financial Interests, Institutional, Research Grant: Ayala, Bristol Myers Squibb, Daiichi Sankyo, Deciphera, Exelixis, Genentech, Novartis, Karyopharm, Merck, Nektar, Pfizer, Xynomic, Bayer, OSI, PF Argentum IP Holdings, Rain Therapeutics, Shasqi; Financial Interests, Personal, Other, Consulting Fees: Synox, Daiichi Sankyo, AVEO, Exelixis, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: Pfizer, GSK, and Boehringer Ingelheim. W.D. Tap: Financial Interests, Personal, Other, Standard budget for site participation: Plexxikon; Financial Interests, Personal, Advisory Board: Eli Lilly and EMD Serono, Certis Oncology Solutions and Innova Therapeutics; Financial Interests, Personal, Invited Speaker, Consulting Fees: Eli Lilly and EMD Serono; Financial Interests, Personal, Invited Speaker, Travel: Eli Lilly and EMD Serono; Financial Interests, Personal, Other, Personal fees and advisory board: Mundipharma, C4 Therapeutics, Daiichi Sankyo, Blueprint, GSK, and Agios Pharmaceuticals, NanoCarrier and Deciphera; Financial Interests, Personal, Other, Personal fees and consulting: Adcendo, Ayala Pharmaceuticals, Kowa, Servier, and AbMaxBio; Financial Interests, Personal, Stocks/Shares: Certis Oncology Solutions, Atropos Therapeutics.∖. J.C. Trent: Financial Interests, Personal, Advisory Board: Blueprint Medicines, Deciphera, Daiichi Sankyo, Epizyme, Agios, C4 Therapeutics, Bayer, AADI Bioscience, LLC, Foghorn Therapeutics, Boehringer Ingelheim, Cogent Medicine, and Servier. H. Gelderblom: Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Deciphera, Novartis, Boehringer Ingelheim, AmMax Bio, Debiopharm, Cytovation, Abbisko. A. Lopez Pousa: Financial Interests, Personal, Other, Site participation in a clinical trial: PharmaMar, Cebiotex, GSK, Eli Lilly, Inmutep and Deciphera. B.A. Van Tine: Financial Interests, Personal, Research Grant: Polaris; Financial Interests, Personal, Other, Consulting Fees: Bayer, Deciphera Pharmaceuticals, Daiichi Sankyo, EcoR1, Advenchen, Putnam, Salarius Pharmaceuticals, Boxer Capital, Acuta Capital Partners, Aadi Biosciences; honoraria for educational talks from Itertion Therapeutics and Total Health Conference; Financial Interests, Personal, Advisory Board: Apexigen, Daiichi Sankyo, Epizyme, Bayer US Medical Affairs, PTC Therapeutics, Aadi Biosciences, Boehringer Ingelheim, Agenus, Regeneron Pharmaceuticals, Advenchen, and Curtis; Financial Interests, Personal, Member of Board of Directors: Polaris; Financial Interests, Personal, Other, Travel: Adaptimmune; Financial Interests, Personal, Other, Patent: Accuronix Therapeutics. M. Rubinacci, K. Tecson, M. Wooddell: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Desai: Financial Interests, Personal, Invited Speaker: Pierre Fabre, Merck KGaA, Novartis, Roche/Genentech, BeiGene, Amgen, AstraZeneca, GSK, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Bayer, GSK, Boehringer Ingelheim, Roche/Genentech, Pfizer, Amgen, Pierre Fabre, BeiGene; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Leadership Role: Australia New Zealand Sarcoma Association. All other authors have declared no conflicts of interest.