T-DXd Yields Meaningful Survival Outcomes in HER2+ Advanced Solid Tumors

Treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) produced clinically meaningful overall survival (OS) and progression-free survival (PFS) benefits among previously treated patients with HER2-expressing advanced solid tumors, according to a press release on findings from the primary analysis of the ongoing phase 2 DESTINY-PanTumor02 trial (NCT04482309).¹

T-DXd also continued to elicit enduring investigator-assessed responses in the primary analysis, further affirming prior findings from an interim analysis of the DESTINY-PanTumor02 trial.

Previous data from the study’s interim analysis included an objective response rate (ORR) of 37.1% across the overall population and 61.3% among those with immunohistochemistry 3+ expression.² Additionally, the agent produced a complete response (CR) rate of 5.6%, a partial response (PR) rate of 31.5%, and a disease control rate (DCR) of 68.2% based on investigator assessment. The median duration of response (DOR) was 11.8 months (95% 9.8-not evaluable [NE]) in the overall population and 22.1 months (95% CI, 9.3-NE) among those with IHC 3+ expression.

T-DXd did not produce any new safety signals at the time of the primary analysis. The incidence and severity of interstitial lung disease (ILD) were comparable with prior trials assessing T-DXd. An independent adjudication committee identified a low rate of grade 5 ILD.

Investigators plan to present data from the DESTINY-PanTumor02 trial at a future medical meeting and discuss their findings with international health authorities.

“The [PFS] and [OS] results for [T-DXd] alongside the continued robust and durable tumor responses seen with further follow up underscore the potential value of this important medicine for patients with HER2-expressing cancers who currently have no targeted treatment options,” Cristian Massacesi, chief medical officer and chief development officer at AstraZeneca, said in the press release. “With a high unmet need in these cancers, we are working with health authorities to bring [T-DXd] to patients with HER2-expressing cancers that could potentially benefit from this medicine as quickly as possible.”

Investigators of the international, multi-center, open-label phase 2 DESTINY-PanTumor02 trial are evaluating T-DXd among patients who received prior treatment for HER2-expressing advanced tumors, including those with bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, and pancreatic cancer. A total of 267 patients are receiving 5.4 mg/kg of T-DXd at treatment sites across Europe, Asia, and North America.

The primary end point of the trial is ORR per RECIST v1.1 criteria. Secondary end points include DOR, DCR, PFS, OS, safety, and pharmacokinetics.

Patients 18 years and older with locally advanced, unresectable, or metastatic disease that has progressed after previous treatment were eligible for enrollment on the trial. Additional eligibility criteria included having adequate cardiac, renal, and hepatic function; tumors expressing HER2; and measurable target disease based on RECIST v1.1 criteria.

Those with a history of non-infectious pneumonitis or ILD requiring treatment with steroids or lung-specific intercurrent clinically significant illnesses were unable to enroll on the study. Patients were also unsuitable for enrollment if they had uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, as well as known somatic DNA mutation of HER2 without tumoral HER2 protein expression.

References

1. Enhertu demonstrated clinically meaningful progression-free survival and overall survival across multiple HER2-expressing advanced solid tumours in DESTINY-PanTumor02 phase II trial. News release. AstraZeneca. July 27, 2023. Accessed July 27, 2023. https://shorturl.at/qDGJT
2. Enhertu demonstrated clinically meaningful and durable responses in patients across multiple HER2-expressing advanced solid tumours. News release. AstraZeneca. June 5, 2023. Accessed July 27, 2023. https://shorturl.at/bdhxB