Jivadco (trastuzumab duocarmazine)

Treatment with T-Duo was manageable, but tolerability was affected by prevalent ocular toxicity, leading to a higher discontinuation rate in the T-Duo arm. T-Duo significantly reduced the risk of progression in patients with advanced HER2+ breast cancer who have progressed during/after ≥2 HER2-targeted therapies or after T-DM1.

P1/2, N=48, Completed, Byondis B.V. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jun 2023 | Trial primary completion date: Dec 2023 --> Apr 2023

Median age was 52 (IQR 44-62), with a median 2 (range 2-6) prior lines of HER2 directed and chemotherapy:86% (25 of 29) had received prior trastuzumab and pertuzumab, 100% (29 of 29) T-DM1 and 3% (1 of 29) patient trastuzumab duocarmazine. These observations warrant further investigations in larger series. The high rate of pneumonitis warrants further consideration.

Moreover, trastuzumab deruxtecan has enhanced the efficacy of trastuzumab emtansine, and the new drug trastuzumab duocarmazine is currently undergoing clinical trials to assess its effect. Lapitinib, neratinib and tucatinib have been approved for HER2-positive metastasis patients, however clinical trials are currently ongoing to optimize combined strategies, to reduce toxicity, and to better define the useful setting. Clinical research should be strengthened along with the discovery and validation of new biomarkers, as well as a deeper understanding of drug resistance and action mechanisms.

Methods The TULIP trial randomly assigned patients with HER2-positive locally advanced or MBC with ≥2 previous HER2-targeting MBC regimens or pretreated with T-DM1, in a 2:1 ratio between T-Duo (1.2 mg/kg q3w) and PC. PC could be either trastuzumab combined with capecitabine or vinorelbine or eribulin or lapatinib plus capecitabine...The final OS results confirm a trend towards a numerically prolonged OS (statistically non-significant) in the T-Duo group compared with PC group. Safety was aligned with the primary analysis, with no new signals identified.

P1, N=32, Completed, Byondis B.V. | Active, not recruiting --> Completed | N=120 --> 32

P3, N=436, Completed, Byondis B.V. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Aug 2022

P1, N=120, Active, not recruiting, Byondis B.V. | Trial completion date: Dec 2023 --> Jun 2023

P2, N=64, Completed, Byondis B.V. | Active, not recruiting --> Completed

Double HER2 blockade with trastuzumab and pertuzumab combined with a taxane achieved an unprecedented survival of over 57 months in first-line patients. Trastuzumab emtansine, the first antibody-drug conjugate approved for patients in second-line treatment was a potent cytotoxic agent bound to trastuzumab and is currently a standard therapeutic strategy. Despite the progress in treatment development, most patients develop resistance and eventually relapse. Advances in the design of antibody-drug conjugates have led to the development of new generation drugs with enhanced properties, such as trastuzumab deruxtecan and trastuzumab duocarmazine, which are significantly changing the paradigm in the treatment of HER2-positive metastatic breast cancer.

P2, N=60, Active, not recruiting, Byondis B.V. | Trial completion date: Dec 2022 --> May 2023 | Trial primary completion date: Dec 2022 --> Apr 2023

P1, N=120, Active, not recruiting, Byondis B.V. | Trial completion date: Jan 2023 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jun 2023