Dana-Farber Tests Safer Cancer Drug Combo in Trial

Combination therapy with trastuzumab deruxtecan and olaparib shows promising activity and tolerability in HER2-expressing malignancies.

Apr. 20, 2026 at 9:26am

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A highly detailed, translucent X-ray-style image revealing the intricate internal structure of a human cell, with a glowing network of DNA strands and cellular components, conceptually illustrating the complex biological processes involved in cancer treatment.An innovative combination therapy aims to precisely target and destroy cancer cells while minimizing harm to healthy tissues.San Diego Today

A phase 1 study by Dana-Farber Cancer Institute found a tolerable dosing schedule for a combination therapy of trastuzumab deruxtecan and olaparib in patients with HER2-expressing advanced and recurrent solid tumors, including ovarian and uterine cancers. The study evaluated 28 participants and identified a regimen with promising anti-cancer activity and reduced toxicity compared to previous trials.

Why it matters

Therapies that reduce systemic toxicity in patients with HER2-expressing advanced solid tumors is a major unmet need. This trial represents a significant step in expanding treatment options for this population by exploring a combination approach that aims to improve both efficacy and tolerability.

The details

The phase 1 trial evaluated 28 participants with HER2-expressing advanced and recurrent solid tumors, including 16 patients with ovarian cancer and 12 with uterine cancer. Participants were given trastuzumab deruxtecan (T-DXd) once every three weeks while gradually increasing the dosage, along with olaparib on continuous or intermittent schedules. Patients in two of the three dosing modules experienced dose-limiting toxicities, but the module 2 treatment schedule and maximum tested dose was found to be tolerable, with only one person experiencing dose-limiting colitis. The combination showed anti-cancer activity across tumor types and HER2 expression levels, with an objective response rate of 54% and a confirmed rate of 46%.

  • The phase 1 trial was initiated by Dana-Farber investigators and reported results at the AACR Annual Meeting 2026, held April 17-22, in San Diego, California.

The players

Dr. Elizabeth Lee

A medical oncologist at Dana-Farber Cancer Institute and the principal investigator of the study.

Dana-Farber Cancer Institute

A comprehensive cancer center in Boston, Massachusetts, that conducted the phase 1 trial evaluating the combination therapy.

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What they’re saying

“The goal is to kill more cancer cells effectively while minimizing damage to healthy cells.”

— Dr. Elizabeth Lee, Principal Investigator

What’s next

The module 2 treatment regimen was selected as the dose that will be evaluated in additional patients in a dose expansion study.

The takeaway

This trial represents a promising step forward in developing combination therapies that can improve the efficacy and tolerability of treatments for patients with HER2-expressing advanced solid tumors, a population with significant unmet medical needs.