Fam-Trastuzumab Deruxtecan-nxki Yields Durable Responses in HER2+ Tumors

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) reached the pre-specified target for objective response rate (ORR) and resulted in long-lasting responses across multiple types of HER2-expressing, heavily pretreated, advanced solid tumors, according to a press release on an analysis of the ongoing phase 2 DESTINY-PanTumor02 trial (NCT04482309).

Investigators of the phase 2 DESTINY-PanTumor02 trial will present data at an upcoming medical meeting and share them with global regulatory authorities.

Investigators will present data at an upcoming medical meeting and share them with global regulatory authorities.

The safety profile observed in patients receiving T-DXd in DESTINY-PanTumor02 was comparable with those reported in previous trials of the agent; investigators identified no new safety signals.

“The clinically meaningful responses seen in the DESTINY-PanTumor02 trial reaffirm our belief in the potential of [T-DXd] across multiple HER2-expressing cancers,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, said in the press release. “The results seen so far across multiple cohorts of the trial will inform next steps of our broad development program as we look to bring this important medicine to as many patients as quickly as possible.”

Investigators of the global, multi-center, multi-cohort, open-label phase 2 DESTINY-PanTumor02 trial are evaluating T-DXd in patients with HER2-expressing tumors across several malignancies including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors.

Investigators have enrolled a total of 268 patients across Asia, Europe, and North America. Patients in each cohort will receive T-DXd at a dose of 5.4 mg/kg.

The primary end point of the trial is investigator-assessed ORR. Secondary end points include duration of response, disease control rate, progression-free survival, overall survival, adverse effects, pharmacokinetics, and immunogenicity as assessed by presence of anti-drug antibodies for T-DXd.

Patients aged 18 to 120 years old with locally advanced, unresectable, or metastatic disease with HER2-expressing tumors determined through local or central assessment were eligible for enrollment on the trial. Additional inclusion criteria included having disease progression following prior treatment; measurable target disease based on RECIST v1.1 criteria; and adequate organ, cardiac, renal, and hepatic function.

Patients with a history of non-infectious pneumonitis requiring treatment with steroids; lung-specific intercurrent clinically significant severe illnesses; or uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals were not able to enroll on the trial. Patients were also unsuitable enrollment if they had known somatic DNA mutation of HER2 without tumoral HER2 protein expression or primary diagnosis of adenocarcinoma of the breast, colon or rectum, gastric body or gastroesophageal junction, or non–small cell lung cancer.

“[T-DXd] has already demonstrated its potential to improve outcomes for patients with HER2-targetable breast, gastric, and lung cancers, and these positive initial results in other tumor settings with significant unmet need are very encouraging. The DESTINY-PanTumor02 results mark an important step forward in our understanding of the potential role of [T-DXd] across multiple HER2-expressing tumor types,” Cristian Massacesi, MD, chief medical officer and oncology chief development officer at AstraZeneca, concluded.

Reference

Enhertu showed clinically meaningful and durable responses across multiple HER2-expressing tumour types in DESTINY-PanTumor02 phase II trial. News release. AstraZeneca and Daiichi Sankyo. March 6, 2023. Accessed March 6, 2023. bit.ly/3L5vC5H