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Haruyasu Murakami
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-41 - A Phase 2 Study of DS-8201a in HER2-Overexpressing or -Mutated Advanced Non-Small-Cell Lung Cancer (ID 12939)
16:45 - 18:00 | Author(s): Haruyasu Murakami
- Abstract
Background
Approximately 30% of non-small-cell lung cancers (NSCLC) are human epidermal growth factor receptor 2 (HER2)-overexpressing (immunohistochemistry [IHC] 2+ or 3+) and approximately 2% have HER2-activating mutations. Although HER2 is considered a potential target for NSCLC, no HER2-targeted therapies are approved for the treatment of NSCLC. DS-8201a is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload (DXd) by a cleavable peptide-based linker, and with a high drug-to-antibody ratio of 7 to 8. In preliminary results from the ongoing phase 1, DS8201-A-J101 trial, DS-8201a (5.6 and 6.4 mg/kg) had a confirmed objective response rate (ORR) of 20.0% (1/5) in HER2-expressing NSCLC (Tsurutani et al, ESMO 2017). In addition to NSCLC, DS-8201a also showed substantial antitumor activity with a manageable safety profile in multiple other HER2-expressing tumors such as breast, gastric, and colorectal cancers.
a9ded1e5ce5d75814730bb4caaf49419 Method
This multicenter, open-label, 2-cohort, phase 2 study will assess the efficacy and safety of DS-8201a in subjects with HER2-overexpressing or -mutated unresectable and/or metastatic nonsquamous NSCLC that is relapsed/refractory to standard treatment or for which no standard treatment is available (NCT03505710). Overall, approximately 80 subjects will be enrolled; 40 subjects in each of 2 cohorts (cohort 1: HER2-overexpressing [IHC 3+ or IHC 2+]; cohort 2: HER2-mutated including exon 20 insertions and single-nucleotide variants in kinase, transmembrane, and extracellular domains [eg, L755S, V659E, S310F]). To be eligible for inclusion in cohort 1, HER2-overexpression must be assessed and confirmed by central testing based on archival samples. To be eligible for inclusion in cohort 2, any HER2-activating mutation must be documented based on archival tumor samples analyzed by Clinical Laboratory Improvement Amendment-certified laboratory or equivalent. All enrolled subjects will receive a 6.4 mg/kg dose of DS-8201a once every 3 weeks; study treatment will be continued until progressive disease or unacceptable toxicity. The primary endpoint is ORR based on RECIST version 1.1 (percentage of complete and partial response) by an independent radiologic facility. Secondary efficacy endpoints include progression-free survival, duration of response, disease control rate, and overall survival. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. The study will enroll subjects in North America, Europe, and Japan. Recruitment began in May, 2018.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-54 - A Historical Comparison of Patients with Advanced NSCLC Harboring Uncommon EGFR Mutations Before and After the Approval of Afatinib in Japan (ID 12711)
12:00 - 13:30 | Author(s): Haruyasu Murakami
- Abstract
Background
Afatinib demonstrated durable responses in patients with metastatic non-small cell lung cancer (NSCLC) harboring uncommon non-resistant epidermal growth factor receptor (EGFR) mutations (G719X, L861Q, and/or S768I) in a pooled analysis of three clinical trials. However, the clinical impact of afatinib therapy in patients with these uncommon EGFR mutations remains unclear.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively evaluated patients with advanced NSCLC whose tumors have uncommon EGFR mutations, and who had received first-line systemic therapy at the Shizuoka Cancer Center between January 2010 and December 2017. Patients with resistant EGFR mutations (T790M, exon 20 insertions) and patients who had received investigational EGFR-TKIs were excluded from this study. Characteristics, therapy regimens and survival outcomes were compared between patients who had received a systemic therapy before (Group A) and after (Group B) the approval of afatinib in Japan. Overall survival (OS) was measured from the first day of first-line systemic therapy until death or the final day of the follow-up period.
4c3880bb027f159e801041b1021e88e8 Result
A total of 23 patients (11 in Group A, and 12 in Group B) were included in this study. The characteristics of the 23 patients were: median age 69 years (range: 41 to 82); 39% male; 26% performance status (PS) 0, 57% PS 1, 13% PS 2 and 4% PS3; 48% with brain metastasis; and 57% current or former smokers. With regard to EGFR mutation type, 30% had G719X, 30% had L861Q, 5% had S768I, 22% had a complex of uncommon mutations, and 13% had both uncommon and common mutations. Patient characteristics were similar in the two groups except for PS. First-line systemic therapy regimens were: gefitinib 73%, erlotinib 9% and platinum-doublet chemotherapy 18% in Group A; gefitinib 8%, erlotinib 25% and afatinib 67% in Group B. Median OS was 10 months for Group A and 25 months for Group B. A significant difference in OS was observed between the two groups (P = 0.018). In a subgroup analysis of patients with PS 0 or 1, there was also a significant difference in OS between the two groups (median, 10 months for Group A vs. 25 months for Group B; P = 0.033).
8eea62084ca7e541d918e823422bd82e Conclusion
After the approval of afatinib in Japan, a majority of patients with advanced NSCLC harboring uncommon EGFR mutations received afatinib therapy as first-line systemic therapy, and it may be related to OS improvement.
6f8b794f3246b0c1e1780bb4d4d5dc53
