362P - Intracranial activity of dacomitinib in treatment naïve advanced EGFR mutated non-small cell lung cancer (NSCLC): Prespecified subgroup analysis of the ATORG-003 trial

Background

Dacomitinib is a second generation EGFR tyrosine kinase inhibitor approved as first-line therapy in advanced EGFR mutated NSCLC. In the phase 3 ARCHER 1050 trial, PFS and OS were improved with dacomitinib compared to gefitinib. However, patients (pts) with central nervous system (CNS) metastases (mets) were ineligible to enroll into the study. ATORG-003 is an ongoing investigator-initiated single-arm phase 2 trial evaluating a dose titration strategy to improve the safety and tolerability of dacomitinib whilst maintaining efficacy. The intracranial activity of dacomitinib was evaluated in a prespecified subgroup analysis.

Methods

ATORG-003 (9 sites, 5 Asian countries) is enrolling newly diagnosed stage IIIB-IV NSCLC pts with EGFR mutations (exon 19 deletion [ex19del] or L858R). Pts receive dacomitinib 30 mg orally once daily for one cycle (4 weeks [wks]), after which pts with grade ≤1 toxicity may escalate to 45 mg once daily (investigator/pt decision). A 24 pt subgroup with asymptomatic/controlled CNS mets completed enrollment in Jun2021. CNS mets were assessed by MRI scan at baseline and every 8 wks for 18 months (mo), then every 12 wks with MRI/CT. Key study secondary endpoints include intracranial objective response rate (iORR) and intracranial progression free survival (iPFS). Analyses were based on 7Jun2022 data cutoff date (median 18.7 mo follow-up).

Results

Of 24 pts with CNS mets, median age was 65 years (range 33-78), ECOG PS 0/1 in 17%/83% and ex19del/L858R/both in 50%/46%/4%. 8/24 (33%) pts had prior intracranial radiotherapy. 2/24 pts dose escalated to 45 mg once daily after Cycle 1. There was measurable (≥10 mm target lesion) CNS mets in 9/24 (38%) pts. The iORR was 67% (1 intracranial CR [iCR], 5 intracranial PR), and median intracranial duration of response (iDoR) was not reached (NR). In 14 pts with non-measurable CNS mets only, iCR was seen in 6 (43%) pts. Median iPFS was NR with only n=5 CNS progression events in the entire cohort and n=7 remain on treatment. Overall (intra and extracranial) ORR was 67% and PFS rate at 12 mo was 42%.

Conclusions

Dacomitinib has significant intracranial activity with observed durable responses in advanced EGFR mutated NSCLC with CNS mets.

Clinical trial identification

NCT04027647.

Editorial acknowledgement

Legal entity responsible for the study

Asian Thoracic Oncology Research Group (ATORG).

Funding

Pfizer.

Disclosure

A. Tan: Financial Interests, Personal, Advisory Board: Amgen, Pfizer, Bayer. D. Kim: Financial Interests, Institutional, Principal Investigator: Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Financial Interests, Institutional, Funding: InnoN, Asia Thoracic Oncology Research Group; Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS/ONO Pharmaceuticals, Daiichi-Sankyo, GSK, Janssen, Merck, MSD, Oncobix, Pfizer, SK Biopharm, Takeda; Financial Interests, Personal, Advisory Role: Scientific advisor for Health insurance review and assessment service, Korea; Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology. T. Baisamut (Reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Invited Speaker: Astrazeneca, Roche, Novartis, MSD. L. Yueh Ni: Financial Interests, Personal, Other, Panel of Discussion for Hepatocellular Carcinoma: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board Meeting for early breast cancer management in our current practice.: Roche; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A multicentre, open-label, single-arm, molecular profiling study of patient with EGFR mutation-positive locally advanced or metastatic NSCLC treated with Osimertinib: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) versus Placebo as Adjuvant Therapy in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation (KEYNOTE-937): MSD; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer: YUHAN; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A phase II randomized study of the combination of Ribociclib plus goserelin acetate with Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with hormone receptor-positive/HER2-negative inoperable locally advanced or metastatic breast cancer - RIGHT Choice Study: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Global, Randomized, Phase 3, Open-Label Study of REGN2810 (Anti-PD-1 Antibody) versus Platinum-Based Chemotherapy in First-Line Treatment of Patients with Advanced or Metastatic PD-L1+ Non-Small Cell Lung Cancer: Regeneron; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3 study to Evaluate Zimberelimab (AB122) Monotherapy Compared to Standard Chemotherapy or Zimberelimab Combined with AB 154 in Front-Line, PD-L1 Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Arcus; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Prospective, Multicenter, Non-Interventional Genomic Profiling Study in Subjects with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) using Foundation Medicine: Roche; Financial Interests, Personal and Institutional, Invited Speaker, Research Title: A Phase 3, randomize, double-blind trial of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) in participants with treatment naive, metastatic non-small cell lung cancer (NSCLC) whose tumors have a tumor proportion score (TPS) greater than or equal to 1% (LEAP-007): MSD. G.F. Ho: Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Merck & Co., Inc., Novartis, Roche, Boehringer Ingelheim; Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: EliLily, Regeneron, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer; Non-Financial Interests, Institutional, Product Samples: Pfizer, Eli Lilly, Novartis, Janssen Pharmaceuticals. L.M. Tho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer. N. Prasongsook: Financial Interests, Personal, Advisory Board: Roche (Thailand), Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, PER, Daz Group, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Merck Pharmaceuticals HK Ltd., MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Da Volterrra, F. Hoffmann-La Roche Ltd./Genentech, Gilead Sciences, Lucence Health Inc., Medscape LLC / WebMD, MiRXES, OSE Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech; Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group; Financial Interests, Personal, Invited Speaker, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Personal, Advisory Role: geneDecode; Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.; Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Personal, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). D.S.W. Tan: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Advisory Role: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-Lilly, Loxo, GlaxoSmithKline, MSD; Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Bayer, Pfizer, Amgen. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli-Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. All other authors have declared no conflicts of interest.