Dr Han on the Investigation of Neoadjuvant Therapy Plus a Dendritic Cell Vaccine in HER2+ Breast Cancer

Heather Han, MD, research director, Department of Breast Oncology, Moffitt Cancer Center, discusses initial safety and efficacy results from the phase 2 NATASHA trial (NCT05325632) in patients with early-stage HER2-positive breast cancer.

The phase 1/2 neoadjuvant study aimed to optimize the efficacy of neoadjuvant therapy by adding a HER2-directed intratumoral dendritic cell (IT-DC1) therapy to the combination of paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta) in patients with HER2-positive breast cancer. Administration of a dendritic cell vaccine prior to treatment with an IgG1 antibody-mediating agent was hypothesized to drive tumor regression and improve immune stimulation without increasing toxicity, Han explains.

Twelve patients were enrolled onto the initial safety lead-in portion of the trial, Han continues. Patients were given DC1 plus trastuzumab and pertuzumab for 6 weeks, followed by 12 weeks of paclitaxel, trastuzumab, and pertuzumab, Han describes. DC1 was administered at doses of either 5.0 x 107 or 10.0 x 107 cells, she notes, adding that patients underwent blood collection at baseline and after the 6 weeks of vaccine administration. MRIs were also performed at baseline, prior to immunotherapy administration, and after chemotherapy administration, Han adds.

Results from the phase 1 portion of the study showed that both DC1 dose level cohorts demonstrated robust radiologic tumor responses, Han reports. Notably, the higher DC1 dose level led to a consistent decrease in peripherally circulating anti-HER2 T-cell response at week 6 vs the lower dose level, Han says. However, this could be attributed to increased T-cell trafficking at the tumor site, she explains.

Additionally, 7 patients who completed surgery (n = 11) experienced a pathologic complete response (pCR), Han details. Of the remaining 4 patients, 1 patient displayed a residual cancer burden (RCB) score of 1, 2 had a score of 2,and 1 had a score of 3. Assessment of radiologic responses per a breast MRI showed that 3 patients experienced a complete response, 8 had a partial response, and 1 achieved stable disease.

Disclosures: Dr Han reports grants from/contracts with AbbVie, GSK, G1 Therapeutics, Quantum Leap Healthcare Collaborative, Pfizer, Zymeworks, Department of Defense, Arvinas, Celcuity, and Marker; consulting fees from Eli Lilly; institutional research funding from Mersana Therapeutics; and data safety monitoring board/advisory board roles with Novartis, AstraZeneca, and Gilead.