Abstract 36P
Background
Selpercatinib, a highly selective RET kinase inhibitor with CNS activity, is approved in multiple countries for patients (pts) with RET fusion-positive NSCLC. In other oncogene-addicted NSCLC settings, targeted treatment beyond RECIST progression (PD) in the case of oligo-progression (oligoPD) is commonly utilized and endorsed by guidelines. We hypothesized that the pattern of PD would be associated with outcomes on post-PD therapy.
Methods
NSCLC pts were treated on the phase I/II LIBRETTO-001 trial (NCT03157128) and were permitted to continue selpercatinib beyond investigator (INV) assessed PD if the pt derived ongoing benefit according to the INV and with sponsor approval. Data of pts with PD confirmed by Blinded Independent Central Review (BICR) were used for this analysis (n=80; data cut of 13JAN2023). OligoPD was defined as up to 5 progressing lesions (1-2 [limited] versus 3-5).
Results
80 pts had BICR-confirmed PD and continued selpercatinib per INV assessment; 23 had widespread progression and 57 pts had oligoPD, including 20 pts with 1-2 progressing lesions and 37 pts with 3-5 progressing lesions. At study entry 11 pts out of 80 pts had CNS metastases. Median duration of treatment (mDoT) post-PD (Table) was longest in pts with limited oligoPD and shortest in pts with widespread PD. Post progression mDoT appeared comparable between pts who progressed in CNS only (n=8) versus pts with extracranial (n=68) PD. Of 80 pts with PD, 33 pts received local radiotherapy upon BICR confirmed progression, further analysis for whom is ongoing. No new safety signals were identified in this population. Table: 36P
| PD per BICR | Pts (n) | mDoT prior to BICR PD (months) | mDoT post-BICR PD (months) |
| All pts treated post-PD | 80 | 9.0 | 5.9 |
| Pts with oligoPD | 57 | 10.9 | 9.4 |
| Pts with 1-2 new/progressive lesions | 20 | 10.5 | 14.6 |
| Pts with 3-5 new/progressive lesions | 37 | 10.9 | 4.8 |
| Pts with widespread PD | 23 | 5.5 | 3.7 |
| Pts with CNS only PD | 8 | 10.4 | 7.5 |
| Pts with extracranial PD | 68 | 8.6 | 6.4 |
Conclusions
Continuing selpercatinib beyond progression may be considered based on INV assessed benefit, particularly for pts with limited oligoPD, including pts with CNS progression. Clinical judgement of ongoing benefit together with radiological imaging should be used to make the most appropriate decision for pts in the setting of PD.
Clinical trial identification
NCT03157128.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Loxo Oncology.
Disclosure
M.J. De Miguel Luken: Financial Interests, Institutional, Invited Speaker: Janssen, MSD; Non-Financial Interests, Personal, Principal Investigator: Janssen, MSD, Roche, PharmaMar, Replimune, Novartis, AbbVie, Achilles, Amunix, Arcus, Furmo, Biontech, Catalym, Dizal, Genentech, Loxo, Numab, Seagen. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal Therapeutics. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics. P. Peterson, S. Szymczak, T. Puri: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Invited Speaker: Novartis. All other authors have declared no conflicts of interest.