57MO - Impact of nirogacestat (niro) on patient-reported outcomes (PROs) in adults with desmoid tumor with a best overall response (BOR) of stable disease (SD): Post hoc analysis from the DeFi study

Background

Desmoid tumors (DT) are rare, soft-tissue tumors associated with a potentially debilitating burden. Niro—a targeted gamma secretase inhibitor—is the first systemic treatment for DT approved in the US. In the phase 3 DeFi study, niro demonstrated statistically significant and clinically meaningful improvement vs placebo (pbo) in progression-free survival (PFS), objective response rate (ORR), and PROs of pain, DT-specific symptom burden, physical and role functioning, and overall quality of life (QoL). As DT can have an unpredictable disease course, an improvement in PROs during SD is important to assess, especially during systemic therapy.

Methods

DeFi was a global, multicenter, double-blind study to determine the efficacy, safety, and tolerability of niro in adults with progressing DT. Patients were randomized to receive niro (150 mg) or pbo twice-daily taken in continuous 28-day cycles. Primary endpoint was PFS; key secondary endpoints were ORR by RECIST 1.1 and change from baseline in PROs (BPI-SF, GODDESS, and EORTC QLQ-C30) at treatment Cycle 10. Post hoc analyses of PROs were conducted in patients with a BOR of SD (07Apr2022 datacut).

Results

ORR was significantly greater with niro (29/70 [41%]) than pbo (6/72 [8%]; P<0.001). A total of 35/70 (50%) niro-group patients had a BOR of SD vs 55/72 (76%) pbo-group patients. Niro-treated patients with a BOR of SD had significantly greater improvement from baseline in all PROs at Cycle 10 than pbo (Table).

Table: 57MO

^aNegative = improve; ^bPositive = improve; ^cBL n=54; ^dBL n=53. BL, baseline.

Conclusions

In this post hoc analysis of the DeFi study, patients that achieved RECIST SD as BOR had significantly greater improvement with niro than pbo in pain and DT-specific symptom burden, physical and role functioning, and overall QoL. These results suggest that niro can provide clinically meaningful benefits for patients with DT, including those with RECIST SD as best response.

Clinical trial identification

NCT03785964.

Editorial acknowledgement

Writing and editing support was provided by Jacqueline Benjamin (Prescott Medical Communications Group; Chicago, IL), with funding from SpringWorks Therapeutics, Inc.

Legal entity responsible for the study

SpringWorks Therapeutics, Inc.

Funding

SpringWorks Therapeutics, Inc.

Disclosure

S. Stacchiotti: Financial Interests, Personal, Advisory Board: Bayer, Daiichi Sankyo, Ikena, Regeneron, NEC Oncoimmunity AS, Pharma Essentia; Financial Interests, Personal, Other, Travel Coverage to scientific conference: PharmaMar; Financial Interests, Personal, Advisory Board, Advisory board meeting: Agenus; Financial Interests, Personal, Advisory Board, Advisory board meetings: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Lectures: Gentili; Financial Interests, Personal, Advisory Board, Advisory Board: Servier; Financial Interests, Institutional, Invited Speaker: Advenchen, Bayer, Deciphera, Epizyme, Daiichi Sankyo, GSK, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc, Inhibrix, Inhbrix; Financial Interests, Institutional, Funding: Blueprint, Novartis; Financial Interests, Institutional, Other, Co-investigator in clinical study: Boehringer Ingelheim; Non-Financial Interests, Personal, Member of Board of Directors, Secretary: Connective Tissue Oncology Society; Non-Financial Interests, Personal, Advisory Role: Chordoma Foundation, Epithelioid HaemangiondotheliomaFoundation, DesmoidFoundation, Epithelioid Hemangioendothelioma (EHE) Rare Cancer Charity (UK); Non-Financial Interests, Personal, Other, Secretary: EORTC soft tissue and bone sarcoma group; Non-Financial Interests, Personal, Leadership Role, President: Italian Sarcoma Group. S.P. Chawla: Financial Interests, Personal, Stocks/Shares, Own stocks.: Cellestia pharma; Financial Interests, Personal, Stocks/Shares, Stocks: Adi Biopharma; Financial Interests, Personal, Ownership Interest, Owner and stocks: Counterpoint; Financial Interests, Institutional, Invited Speaker, Clinical research: Amgen; Financial Interests, Institutional, Invited Speaker, Research: Adi bio, NK Gene, BMS, Rain Therapeutic, Shasqui, Monopar, Ayala, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Research: Rain Therapeutic, Molleculin. R. Chugh: Financial Interests, Personal, Funding: SpringWorks Therapeutics, Inc, Ayala, AADi, AstraZeneca, Astex, Cogent, Advenchen, Inhibrx, Epizyme, Pfizer, Plexxikon, Mundipharma, GSK, Qilu Puget Sound, Janssen, Cornerstone, Kronos Bio, PTC Therapeutics; Financial Interests, Personal, Advisory Board: SpringWorks Therapeutics, Inc, Ipsen pharmaceuticals, Deciphera, Inhibrx, Jazz pharmaceuticals. M. Gounder: Financial Interests, Personal, Other, Honoraria: Flatiron Health, PER, Medscape, Guidepoint Global, touchIME, MedLearning Group; Financial Interests, Personal, Advisory Role: More Health, Daiichi Sankyo, Karyopharm Therapeutics, Epizyme, Bayer, Springworks Therapeutics, Boehringer Ingelheim, TYME, Ayala Pharma, Rain Therapeutics, Regeneron; Financial Interests, Personal, Speaker’s Bureau: Amgen, Karyopharm Therapeutics, Boehringer Ingelheim; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Royalties: GODDESS PRO Desmoid Tumor; Financial Interests, Personal, Other, Travel Accommodations: Epizyme. R. Ratan: Financial Interests, Personal, Advisory Board: SpringWorks Therapeutics; Financial Interests, Institutional, Invited Speaker: Ayala Pharmaceuticals, Springworks Therapeutics, C4 Therapeutics. W.T.A. van der Graaf: Financial Interests, Institutional, Advisory Board: PTC Therapeutics, Agenus, SpringworksTx; Financial Interests, Institutional, Invited Speaker, Clinical study: Springworks, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, IIS: Lilly; Financial Interests, Institutional, Invited Speaker, Clinical Study: AYALA; Non-Financial Interests, Personal, Member of Board of Directors, President: EORTC; Non-Financial Interests, Personal, Member of Board of Directors: European Cancer Organisation; Non-Financial Interests, Personal, Member of Board of Directors, Chair: Dutch Sarcoma Group, Dutch AYA 'Young and Cancer' Care Network. V. Amoruccio, T. Bell, S. Cho: Financial Interests, Personal, Full or part-time Employment: SpringWorks Therapeutics, Inc. P. Schöffski: Financial Interests, Personal, Invited Speaker, Speaker, Consultant, Advisor: Deciphera, Ellipses Pharma, Transgene, Exelixis, Boehringer Ingelheim, Studiecentrum voor Kernenergie, SQZ Biotechnology, Adcendo, PharmaMar, Merck Healthcare KGaA, Medpace, Cogent, Eisai, Curio Science, LLX Solutions, Servier, Genmab, Biolumina, Sanofi, Regeneron, Moleculin Biotech, Avacta Life Sciences, Amryt Pharma, UCB, Boxer Capital; Financial Interests, Institutional, Funding: CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, ONA Therapeutics, Adcendo. All other authors have declared no conflicts of interest.