FDA Lifts Hold on Study of XMT-2056 in HER2+ Recurrent/Metastatic Solid Tumors


With the clinical hold lifted by the FDA, the phase 1 trial of XMT-2056 will continue to evaluate the agent's safety, tolerability, and efficacy in patients with HER2-expressing solid tumors.

  • XMT-2056 is a novel Immunosynthen STING-agonist antibody-drug conjugate (ADC) being evaluated in a phase 1 trial (NCT05514717) for patients with HER2-high or -low solid tumors.

  • Following a serious adverse event (SAE), investigators lowered the starting dose of XMT-2056 in the phase 1 trial.

  • The adjustment ensures patient safety while allowing the study to proceed.

The FDA has lifted the clinical hold placed on the phase 1 clinical trial of XMT-2056, a systemically administered Immunosynthen STING-agonist ADC, as monotherapy for the treatment of patients with HER2-high or -low advanced or recurrent solid tumors.1

On March 14, 2023, the FDA placed the clinical hold following a report of a patient who experienced a grade 5 SAE deemed to be related to treatment with XMT-2056 which occurred at the initial dose level in the dose-escalation portion of the trial.2

To address the hold, investigators lowered the phase 1 dose-escalation starting dose. With the hold now lifted, the trial will continue to evaluate XMT-2056 in this patient population.

“An in-depth analysis of cytokine, pharmacokinetic, and other clinical data from patients enrolled in our phase 1 trial indicated that XMT-2056 is a highly potent innate immune agonist,” said Martin Huber, MD, president and chief executive officer of Mersana Therapeutics, in a press release.1 “Based on these data and with patient safety at the forefront of our efforts, we have lowered the starting dose in our phase 1 dose escalation design.”

Previously in 2022, the FDA granted orphan drug designation to XMT-2056 for the treatment of gastric cancer. Also in August 2022, Mersana entered into a global collaboration providing GSK with an exclusive option to co-develop and commercialize XMT-2056. GSK has not exercised this option to date.

About XMT-2056

XMT-2056 targets a novel HER2 epitope and locally activates STING signaling in tumor-resident immune cells, as well as in tumor cells. This agent can potentially treat patients with HER2-high or -low tumors when used alone or in combination with standard-of-care agents.

The multicenter, open-label, phase 1 trial of XMT-2056 is for the treatment of patients with advanced/recurrent solid tumors that were previously treated and are expressing HER2. This includes patients with breast, gastric, colorectal, and non–small-cell lung cancers.

About 171 patients with recurrent or metastatic solid tumors with HER2 expression will be enrolled if they have had disease progression after treatment, are intolerant to treatment, are contraindicated with available anti-cancer therapies, and have an ECOG performance status 0 or 1. Other requirements include measurable disease as defined by RECIST version 1.1and having a fresh tumor biopsy tissue available to submit to a central laboratory.3

In the dose-escalation and dose-expansion portions of the trial, the safety, tolerability, and exposure of XMT-2056 will be evaluated, as well as the preliminary antitumor activity as measured by overall response rate (ORR), duration of response (DOR), and disease control rate (DCR).

The primary end points of the trial include frequency of dose-limiting toxicities, incidence of adverse events, and ORR as assessed by the investigator per RECIST version 1.1. Secondary end points include ORR, DOR, DCR, and pharmacokinetics.

“We are pleased to have aligned with FDA on the path forward and are excited to have the opportunity to continue to investigate the potential of XMT-2056 and our Immunosynthen ADC platform in the clinic,” said Huber in a press release.1

  1. Mersana Therapeutics announces FDA has lifted clinical hold on phase 1 clinical trial of XMT-2056. News Release. Mersana Therapeutics, Inc. October 31, 2023. Accessed November 1, 2023. https://tinyurl.com/mrrjrtnu
  2. Mersana Therapeutics announces clinical hold on XMT-2056 phase 1 clinical trial. News release. Mersana Therapeutics, Inc. March 13, 2023. Accessed November 1, 2023. https://bit.ly/3JdMioW
  3. A study of XMT-2056 in advanced/recurrent solid tumors that express HER2. ClinicalTrials.gov. Updated March 15, 2023. Accessed November 1, 2023. https://tinyurl.com/5dwhcetb
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