trastuzumab deruxtecan (t-dxd; ds-8201) in patients with

Presented on: ASCO20 Virtual, 29.05. - 31.05.2020Presented on: ASCO20 Virtual, 29.05. - 31.05.2020

Trastuzumab Deruxtecan (T-DXd; DS-8201) in Patients With HER2-Mutated MetastaticNon-Small Cell Lung Cancer: Interim Resultsof DESTINY-Lung01Egbert F. Smit, Kazuhiko Nakagawa, Misako Nagasaka, Enriqueta Felip, Yasushi Goto, Bob T. Li, Jose M. Pacheco, Haruyasu Murakami, Fabrice Barlesi, Andreas Saltos, Maurice Perol, Hibiki Udagawa, Kapil Saxena, Ryota Shiga, Ferdinand Guevara, Suddhasatta Acharyya, Javad Shahidi, David Planchard, Pasi A. Jänne

On behalf of the DESTINY-Lung01 investigators

Presented on: ASCO20 Virtual, 29.05. - 31.05.2020

DESTINY-Lung01 Study Design

a Based on local assessment of archival tissue.

Primary endpoint

• Confirmed ORR by independent central review

An open-label, multicenter, phase 2 study (NCT03505710)

Data cutoff: November 25, 2019

• 45.2% of patients (19/42) in Cohort 2 remained on treatment

• 54.8% discontinued, primarily for progressive disease and adverse events (21.4% each)

Patients

• Unresectable/metastatic nonsquamous NSCLC

• Relapsed/refractory to standard treatment

• HER2-expressing or HER2-activating mutationa

• No prior HER2-targeted therapy, except pan-HER TKIs

T-DXd 6.4 mg/kg q3w

Cohort 1 (n = 42)HER2 expressing (IHC 3+ or IHC 2+)

Cohort 2 (n = 42)HER2 mutated


Progression-Free and Overall Survival

a Patients were censored if they discontinued treatment; the median is estimated by Kaplan-Meier analysis.Median follow-up, 8.0 months (range, 1.4-14.2 months). Dashed lines indicate upper and lower 95% Cl.

DESTINY-Lung01 HER2-Mutated NSCLC


Treatment-Emergent Adverse Events in >15% of Patients

a. 2 patients had febrile neutropenia; grade ≥ 3 neutrophil count decreased, 26.2%.



Conclusions

1.Tsurutani J, et al. Cancer Discov. 2020; Mar [epub ahead of print]; 2. Tamura K et al. Lancet Oncol. 2019;20(6):816-826; 3. Modi S, et al. N Engl J Med. 2020;382(7):610-621; 4. Modi S, et al. J Clin Oncol. Feb [epub ahead of print]; 5. Shitara K, et al. Lancet Oncol. 2019;20(6):827-836.

• T-DXd demonstrated clinical activity in this interim analysis with a high ORR and durable responses in patients with HER2-mutated NSCLC

– ORR, 61.9% (95% Cl, 45.6%-76.4%)

– Median DOR not reached

– Estimated median PFS, 14.0 months

• The safety profile in the HER2-mutated cohort was generally consistent with what was previously reported1-5

– Low-grade gastrointestinal and hematologic AEs were most common

– Drug-related ILD events observed in this patient population were low grade, and there were no deaths. However, ILD remains an important identified risk for patients treated with T-DXd and requires careful monitoring and management

• These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated NSCLC

• Enrollment in this HER2-mutated cohort was expanded with an additional 50 patients to better characterize the risk-benefit ratio of T-DXd in patients with HER2-mutated NSCLC


trastuzumab deruxtecan (t-dxd; ds-8201) in patients with

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