Phase 1B Study of XMT-1660 Starts Dosing Patients With Breast, Endometrial and Ovarian Tumors

Dosing of the investigational antibody-drug conjugate (ADC) XMT-1660 has begun in a phase 1 study of patients with breast cancer, endometrial cancer, and ovarian cancer.¹

XMT-1600 targets B7-H4 and has a precise drug-to-antibody ratio, according to Mersana Therapeutics, Inc. Overexpression of B7-H4 is common in many cancers, including breast, endometrial, and ovarian cancer.¹

“The initiation of this phase 1 trial represents an important milestone for Mersana as we continue to build our pipeline across three ADC platforms and seek to further demonstrate the potential of our Dolalock payload and Dolasynthen platform,” said Anna Protopapas, president, and chief executive officer of Mersana Therapeutics. “Based on our promising preclinical data, we believe XMT-1660 has the potential to serve as a highly impactful cancer treatment.

The phase 1b, first-in-human, dose escalation and expansion, multicenter study (NCT05377996) will have a dose-escalation and dose-expansion portion. The co primary end points to be assessed during the dose-escalation phase are the frequency of dose-limiting adverse events (AEs) to determine the recommended phase 2 dose, and the incidence of AEs to determine the safety and tolerability of the agent. The coprimary end point to be evaluated during the dose-expansion phase include safety/tolerability, objective response rate (ORR), and duration of response (DOR).²

Secondary end points explored during the study include ORR, DOR, and time of maximum observed plasma concentration. In addition, the study will assess the area under the concentration-time curve of XMT-1660, systemic clearance of the agent, apparent terminal elimination half-life, volume distribution, trough concentration of XMT-1660, and antibodies and neutralizing antibodies.

To be eligible for the study, patients must have proven recurrent or advanced disease that has progressed after treatment with available anti-cancer therapies. Patients must also have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1, and be willing to undergo a minimally invasive tumor biopsy for testing.

The study excludes patients who have been previously treated with an ADC containing an auristatin or maytansinoid payload or had major surgery within 28 days of treatment starting in the study. Patients diagnosed with an additional malignancy requiring active treatment, those with current severed, uncontrolled systemic disease, and those with central nervous system metastases are excluded from the study.

Patients with breast, endometrial, or ovarian cancer, including those with fallopian tube or primary peritoneal cavity tumors, are being recruited at sites in New York, Virginia, and Washington.

“We are excited to begin investigating how it may benefit patients in a range of cancers with high unmet needs, said Protopapas, in the press release.¹

_REFERENCES:

_{1. Mersana Therapeutics announces initiation of phase 1 trial of XMT-1660 in breast, endometrial and ovarian cancers. News release. Mersana Therapeutics. August 16, 2022. Accessed August 17, 2022. https://bit.ly/3PKi12p}

_{3. A study of XMT-1660 in participants with solid tumors. Clinicaltrials.gov. Updated July 13, 2022. Accessed August 17, 2022.}