849O - Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent/metastatic salivary gland cancer: Results from the MYTHOS trial

Background

Trastuzumab deruxtecan (T-DXd) is a HER2-targeting ADC approved for patients (pts) with HER2-positive (+ve)/-low breast, HER2 +ve gastric, or HER2-mutated non-small cell lung cancer. This April, the FDA approved it for HER2 +ve (only IHC 3+) solid tumors. The MYTHOS trial (jRCT2011210017) is the first phase II study of T-DXd in HER2 +ve (IHC 3+ or IHC 2+/ISH+) or -low (IHC 1+ or IHC 2+/ISH-) salivary gland cancer (SGC). We herein report the results of the HER2 +ve cohort.

Methods

Pts with recurrent/metastatic (RM) SGC with centrally confirmed IHC3+ or IHC 2+/ISH+ were eligible for the HER2 +ve cohort. The pts received T-DXd 5.4 mg/kg every 3 weeks. The primary endpoint was ORR using RECIST v1.1 assessed by BIRC. Secondary endpoints included DCR, PFS, OS, and safety. This study required 19 pts, based on a threshold ORR of 25%, an expected ORR of 65%, 90% power, and a two-sided alpha value of 0.05 using the binomial test, assuming 2 dropout pts.

Results

A total of 19 pts with RM HER2 +ve SGC were enrolled. Median age was 65 (range 48-76), 4 pts were female, and all had performance status 0-1. The histology of all pts was salivary duct carcinoma. Sixteen pts had HER2 IHC 3+ tumors, and 3 had HER2 IHC 2+/ISH+ tumors. All pts were previously treated. Fourteen pts had curative treatment (13 surgery and 1 radiotherapy). Seventeen pts received systemic therapy for RM disease, including 8 pts treated with trastuzumab. ORR by BIRC was 68.4% (13/19; 95% CI, 43.4-87.4). DCR was 100% (19/19; 95% CI, 82.4-100). Median PFS was 15.9 months (95% CI, 5.8-NE). No patients had died at a median follow-up of 15.0 months. Common grade 3/4 adverse events (> 10%) were neutropenia (31.6%), lymphopenia (15.8%), and anemia (15.8%). Drug-related interstitial lung disease (ILD)/pneumonitis occurred in 7 pts (36.8%; grade 1/2 in 6 pts, grade 3 in 1 pt). Five pts (26.3%) discontinued treatment due to drug-related AEs, all of which were ILD. No drug-related death occurred.

Conclusions

This study demonstrated encouraging efficacy and manageable toxicities for T-DXd, including ILD, consistent with the known profile of Japanese population, suggesting that T-DXd could be an effective treatment option in pts with HER2 +ve RM SGC.

Clinical trial identification

jRCT2011210017 (release date: June 17, 2021).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Daiichi Sankyo.

Disclosure

I. Kinoshita: Financial Interests, Personal, Invited Speaker, Invited Speaker: MSD Pharmaceutical; Financial Interests, Personal, Invited Speaker, Invited Speaker, chairperson of lecture: Bayer; Financial Interests, Personal, Invited Speaker, Invited Speaker: Takeda Pharmaceutical, Konica Minolta Realm; Financial Interests, Personal, Other, chairperson of lecture: Chugai Pharma, Novartis Pharma, Guardant Health Japan; Financial Interests, Personal and Institutional, Local PI, local PI: Daiichi Sankyo; Financial Interests, Personal And Institutional, Research Grant, Research Grant: Konica Minolta Realm; Financial Interests, Personal and Institutional, Local PI, Local PI: Eisai. Y. Honma: Financial Interests, Personal, Advisory Board: Janssen, Rakuten Medical Japan; Financial Interests, Personal and Institutional, Coordinating PI: Taiho Pharmaceutical, Chugai Pharma, MSD, Jannsen, Merck Biopharma; Financial Interests, Institutional, Coordinating PI: GSK, Adlai Nortye Biopharma, Maruho, Genmab, Astellas pharma, AstraZeneca; Financial Interests, Institutional, Funding: Rakuten Medical Japan. N. Kiyota: Financial Interests, Personal, Invited Speaker: Ono pharmaceutical, Bristol Myers Squibb, Bayer, MSD, Eisai, Lilly, Novartis, Merck Biopharma; Financial Interests, Institutional, Local PI: Ono pharmaceutical, AstraZeneca, Rakuten Medical, Roche, Bayer, Boehringer Ingelheim, Lilly, Abbvie, GSK; Financial Interests, Institutional, Steering Committee Member: Adlai Nortye. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono pharma, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eisai, Novartis; Financial Interests, Institutional, Local PI: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol Myers Squibb, Loxo, GSK, Lilly, Rakuten Medical, Bayer, Merck Biophama; Financial Interests, Institutional, Research Grant: Bayer. S. Takahashi: Financial Interests, Personal, Invited Speaker: MSD, Eisai, Daiichi Sankyo, Chugai, Bayer, Ono, Taiho, Astellas, Sanofi, Asahikasei; Financial Interests, Institutional, Local PI: Taiho, Daiichi Sankyo, Novartis, Ono Pharmaceutical, Eisai, IQVIA, Bristol Myers Squibb, Bayer, AstraZeneca, Eli Lilly. Y. Hatanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly; Financial Interests, Institutional, Research Grant: NEC, Eli Lilly, Daiichi Sankyo, Shionogi, Konica Minolta. H. Dosaka-Akita: Financial Interests, Institutional, Research Grant: Daiichi Sankyo Co Ltd, Taiho Pharmaceutical Co Ltd, Chugai Pharmaceutical Co Ltd. All other authors have declared no conflicts of interest.