LBA62 - Efficacy and safety of patritumab deruxtecan (U3-1402), a novel HER3 directed antibody drug conjugate, in patients (pts) with EGFR-mutated (EGFRm) NSCLC

Background

There are few treatment options for pts with advanced EGFRm NSCLC after failure of EGFR TKI and platinum-based chemotherapy. We report safety and activity in such pts treated in a phase I study (NCT03260491) with patritumab deruxtecan, a HER3 directed antibody drug conjugate, at the 5.6 mg/kg recommended dose for expansion.

Methods

The dose escalation part was presented previously. The dose expansion part enrolled pts with EGFRm NSCLC with prior EGFR TKI and platinum-based chemotherapy. Primary objective is assessment of activity by confirmed ORR (blinded independent central review, BICR); secondary objectives include evaluation of safety. Patritumab deruxtecan was administered IV Q3W.

Results

As of 30 April 2020, 57 pts from dose escalation and dose expansion were treated at the 5.6 mg/kg dose, and 56 pts were evaluable for response. Among 28 pts continuing treatment at data cutoff, 6 had only 1 tumor evaluation. Median prior anticancer regimens for metastatic disease was 4 (range, 1-9); 51 pts [90%] received prior platinum. Median number of prior EGFR TKIs was 2 (range, 1-4); 49 pts [86%] received prior osimertinib. 27 pts (47%) had history of central nervous system metastases. Median treatment duration was 3.5 mo (range, 1-14 mo); median follow up was 5.4 mo (range, 0.3-15 mo). The most common grade ≥3 treatment-emergent adverse events were platelet count decrease (25%) and neutrophil count decrease (16%). Efficacy for the 56 efficacy-evaluable pts is shown below; 3 additional pts had PR awaiting confirmation. HER3 was expressed in nearly all tumors. Efficacy was observed in pts with various mechanisms of EGFR TKI resistance, including EGFR C797S, MET amp, HER2m, BRAF fusion, and PIK3CAm.

Conclusions

Patritumab deruxtecan at 5.6 mg/kg provides promising evidence of preliminary antitumor activity and safety in heavily pretreated pts with locally advanced or metastatic EGFRm NSCLC. Table: LBA62

Activity according to BICR evaluation (Efficacy-Evaluable Population)

^a22/56 (39%) patients had best percentage decrease in sum of tumor diameters ≥30%. BOR, best overall response; CR, complete response; DCR, disease control rate; DoR, duration of response; NE, not evaluable; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.

Clinical trial identification

NCT03260491.

Editorial acknowledgement

Jessica R. Augello, Ashfield Healthcare Communications.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

H.A. Yu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Cullinan; Research grant/Funding (institution): Lilly. K. Gold: Advisory/Consultancy: Rakuten; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Pharmacyclics; Research grant/Funding (self): BerGenBio; Research grant/Funding (self): Daiichi-Sankyo. H. Hayashi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca K.K.; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer Ingelheim Japan Inc; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Co. Ltd.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharmaceutical Co. Ltd.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly Japan K.K.; Speaker Bureau/Expert testimony: Kyorin Pharmaceutical; Speaker Bureau/Expert testimony: MSD K.K.; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Pfizer Japan Inc.; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co. Ltd.; Advisory/Consultancy: Shanghai Haihe; Advisory/Consultancy: Biopharm. M. Johnson: Research grant/Funding (institution): BerGenBio, Research grant/Funding (institution): Lilly, Research grant/Funding (institution): EMD Serono, Research grant/Funding (institution): Janssen, Research grant/Funding (institution): Mirati Therapeutics, Research grant/Funding (institution): Genmab, Research grant/Funding (institution): Pfizer, Research grant/Funding (institution): AstraZeneca, Research grant/Funding (institution): Genentech / Roche, Research grant/Funding (institution): Stemcentrix, Research grant/Funding (institution): Novartis, Research grant/Funding (institution): Checkpoint Therapeutics, Research grant/Funding (institution): Array BioPharma, Research grant/Funding (institution): Regeneron, Research grant/Funding (institution): Apexigen, Research grant/Funding (institution): AbbVie, Research grant/Funding (institution): Tarveda, Research grant/Funding (institution): Adaptimmune, Research grant/Funding (institution): Syndax, Research grant/Funding (institution): Neovia, Research grant/Funding (institution): Boehringer Ingelheim, Research grant/Funding (institution): Sanofi, Research grant/Funding (institution): Hengrui Therapeutics Inc., Research grant/Funding (institution): Merck, Research grant/Funding (institution): Daiichi - Sankyo, Research grant/Funding (institution): Lycera, Research grant/Funding (institution): G1 Therapeutics, Research grant/Funding (institution): Dynavax, Research grant/Funding (institution): Loxo, Research grant/Funding (institution): Cytomx, Research grant/Funding (institution): BeiGene, Research grant/Funding (institution): Birdie, Research grant/Funding (institution): Corvus, Research grant/Funding (institution): Incyte, Research grant/Funding (institution): Genocea, Research grant/Funding (institution): Gritstone, Research grant/Funding (institution): Amgen, Research grant/Funding (institution): Bristol Myers Squibb, Research grant/Funding (institution): Kadmon, Research grant/Funding (institution): Clovis, Research grant/Funding (institution): Acerta, Research grant/Funding (institution): OncoMed, Research grant/Funding (institution): Guardant Health, Research grant/Funding (institution): Takeda, Research grant/Funding (institution): Shattuck Labs, Research grant/Funding (institution): GlaxoSmithKline; Consulting/Advisory Role (spouse): Contract Lobbyist for Astellas, Consulting/Advisory Role (spouse): Contract Lobbyist for Otsuka Pharmaceuticals; Consulting/ advisory Role (self) - all to institution: Genentech/Roche, Consulting/ advisory Role (self) - all to institution: Celgene, Consulting/ advisory Role (self) - all to institution: Boehringer Ingelheim, Consulting/ advisory Role (self) - all to institution: Sanofi,Consulting/ advisory Role (self) - all to institution: Mirati, Consulting/ advisory Role (self) - all to institution: Loxo, Consulting/ advisory Role (self) - all to institution: Calithera, Consulting/ advisory Role (self) - all to institution: AstraZeneca, Consulting/ advisory Role (self) - all to institution: Merck, Consulting/ advisory Role (self) - all to institution: Araxes Pharma, Consulting/ advisory Role (self) - all to institution: Mersana Therapeutics, Consulting/ advisory Role (self) - all to institution: BeiGene, Consulting/ advisory Role (self) - all to institution: Incyte, Consulting/ advisory Role (self) - all to institution: Pfizer, Consulting/ advisory Role (self) - all to institution: Guardant Health, Consulting/ advisory Role (self) - all to institution: Bristol Myers Squibb, Consulting/ advisory Role (self) - all to institution: Ribon Therapeutics; Travel/Accommodation/Expenses: AbbVie, Travel/Accommodation/Expenses: Astellas, Travel/Accommodation/Expenses: AstraZeneca, Travel/Accommodation/Expenses: Boehringer Ingelheim, Travel/Accommodation/Expenses: Clovis, Travel/Accommodation/Expenses: Daiichi Sankyo, Travel/Accommodation/Expenses: EMD Serono, Travel/Accommodation/Expenses: Bristol Myers Squibb, Travel/Accommodation/Expenses: Exelixis, Travel/Accommodation/Expenses: Genentech, Travel/Accommodation/Expenses: Incyte, Travel/Accommodation/Expenses: Merck, Travel/Accommodation/Expenses: Pfizer, Travel/Accommodation/Expenses: Sysmex Inostics, Travel/Accommodation/Expenses: Vapotherm. M. Koczywas: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Celgene. H. Murakami: Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Chugai Pharma; Speaker Bureau/Expert testimony: Lilly Japan; Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: MSD. M. Nishio: Speaker Bureau/Expert testimony, Research grant/Funding (self): Chugai Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Taiho Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer-Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (self): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo Healthcare; Research grant/Funding (self): Merck Serono; Research grant/Funding (self): Astellas. C. Steuer: Honoraria (self): AbbVie; Honoraria (self): Bergen Bio; Honoraria (self): Eli Lilly; Honoraria (self): Armo. J. Yang: Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Celgene; Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Yuhan; Advisory/Consultancy: Hansoh; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Takeda Oncology; Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Eli Lilly. S. Karam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. Z. Qi: Full/Part-time employment: Daiichi Sankyo. S. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. C. Yu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo. P.A. Jänne: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Acea Biosciences; Advisory/Consultancy: Ignyta; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Loxo Oncology; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly Pharmaceuticals; Advisory/Consultancy: Araxes Pharmaceuticals; Advisory/Consultancy: SFJ Pharmaceuticals; Advisory/Consultancy: Voronoi; Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Advisory/Consultancy: Biocartis; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (self): Takeda Oncology; Advisory/Consultancy: Mirati Therapeutics; Shareholder/Stockholder/Stock options: Gatekeeper Pharmaceuticals; Research grant/Funding (self): Astellas Pharmaceuticals; Research grant/Funding (self): Puma; Research grant/Funding (self): Revolution Medicines; Licensing/Royalties: LabCorp. All other authors have declared no conflicts of interest.