Three early-phase studies presented at the IASLC 2020 World Conference on Lung Cancer point to the potential of antibody–drug conjugates for the treatment of different populations of patients with advanced non-small-cell lung cancer.

The authors continue: “To our knowledge, this study is the first randomised trial to show a significant benefit of one antibody-drug conjugate treatment in patients who have progressed on another antibody-drug conjugate, providing an optimistic outlook for sequential antibody-drug conjugate treatments to improve disease outcomes in patients with HER2-positive metastatic breast cancer and other patient populations.”

Cohort 3 – Sacituzumab govitecan 10 mg/kg on days 1 and 8 of a 28-day cycle plus pembrolizumab 200 mg on day 1 of a 21-day cycle. https://clinicaltrials.gov/ct2/show/NCT03547973 Sponsor: Gilead Sciences Interim findings for Cohort 3 of the open-label TROPHY-U-01 trial for the Trop-2-directed antibody–drug conjugate sacituzumab govitecan plus pembrolizumab were presented at the ASCO GU 2022  meeting, showing an “encouraging” ORR and clinical benefit rate for the combination of sacituzumab govitecan and pembrolizumab, at 34% and 44%, respectively.

Hope Rugo outlines the latest results from the TROPiCS-02 trial of sacituzumab govitecan in hormone receptor-positive, HER2-negative advanced breast cancer and discusses where the antibody–drug conjugate fits into the treatment paradigm.

The surgical outcomes are pending for 24% of patients who received T-DXd alone and 31% of those who received the antibody–drug conjugate alongside anastrozole, said the presenter.

Of the 42 adults in the study assigned to receive the Met-targeted antibody–drug conjugate teliso-v 2.7 mg/kg every 21 days plus erlotinib 150 mg/day, 36 had evaluable disease; 28 had disease positive for c-Met overexpression, a MET exon 14 skipping mutation, or MET amplification, as well as for EGFR mutations.

The median OS durations were 14.4 and 11.2 months for sacituzumab govitecan and chemotherapy, respectively, and equated to a 21% reduction in the risk for death with the use of the antibody–drug conjugate.

The latest findings from the EV-103 study add support for the first-line use of enfortumab vedotin plus pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

Jonathan Rosenberg presents data from a randomized noncomparative cohort of the EV-103 trial of enfortumab vedotin, investigating the agent alone or together with pembrolizumab as a first-line option for cisplatin-ineligible patients with advanced urothelial carcinoma. This independent video interview was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

DESTINY-Lung02 trial findings indicate that reducing the dose of trastuzumab deruxtecan can improve the antibody–drug conjugate’s toxicity profile without loss of activity in patients with previously treated, metastatic HER2 -positive non-small-cell lung cancer.

The antibody–drug conjugate trastuzumab deruxtecan induces a high intracranial response rate among women with HER2-positive breast cancer and active brain metastases, TUXEDO-1 study findings indicate.

A pooled analysis of nine early-phase trials of trastuzumab deruxtecan monotherapy has identified an incidence of drug-related interstitial lung disease/pneumonitis of 15.4%.

The researchers explain that pneumonitis was not considered an adverse event of special interest in the EV-201 and EV-301 trials of the antibody–drug conjugate for metastatic urothelial cancer.

The HER2-directed antibody–drug conjugate can be given to breast cancer patients with unresectable or metastatic HER2-low disease – defined as an immunohistochemistry score of 1+, or 2+ but with negative in situ hybridization – who have received prior chemotherapy in the metastatic setting or relapsed during or within 6 months of finishing adjuvant chemotherapy.

DOI [Teaser] Key Points Trastuzumab deruxtecan antibody drug conjugate can lead to a life-threatening interstitial lung disease/pneumonitis.

Andrea Apolo and Elizabeth Plimack discuss highlights of the ASCO 22 Annual Meeting. Here, they talk about some of the exciting new data presented on the use of antibody-drug conjugates targeting HER2, which are starting to show promise for the treatment of urothelial carcinoma (UC).  This independent video interview was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

The researchers therefore evaluated T-DXd – a next-generation, HER2-directed antibody–drug conjugate with a unique mechanism of action, including the bystander effect – in this patient population, recruiting 557 patients who had received one or two lines of chemotherapy prior to inclusion in the phase 3 trial.