XMT-1660 for Breast Cancer

Recruiting at 26 trial locations

Overseen By Caroline Rogalski

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mersana Therapeutics

Must not be taking: Auristatin ADCs

Disqualifiers: Untreated CNS metastases, Cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

319 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XMT-1660, an antibody-drug conjugate, for individuals with advanced or recurring solid tumors, such as certain types of breast cancer. The primary goal is to determine the safety of XMT-1660 and its effect on tumors. Suitable candidates have a solid tumor unresponsive to other treatments and may experience recurring tumors or brain-related symptoms. Participants must be willing to provide a sample of their tumor tissue for testing. The study seeks to discover a new method to aid those whose cancer does not respond to current treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had major surgery or certain cancer treatments recently, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that XMT-1660 is likely to be safe for humans?

Previous studies indicate that patients treated with XMT-1660, also known as emiltatug ledadotin, generally tolerate the treatment well. Research shows that its safety remains manageable, even for patients who have undergone multiple treatments for breast cancer. Although specific side effects are not detailed, the overall findings suggest that potential benefits outweigh any negative effects. This makes XMT-1660 a promising option for further study. This information is important for those considering participation in a clinical trial involving XMT-1660. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

XMT-1660 is unique because it represents a new approach to treating breast cancer. Unlike traditional chemotherapy, which attacks both cancerous and healthy cells, XMT-1660 is designed to be more selective, potentially reducing side effects. It works as an antibody-drug conjugate (ADC), which means it combines an antibody with a cancer-fighting drug to specifically target cancer cells. This targeted mechanism allows for a more precise treatment, sparking excitement among researchers for its potential to improve outcomes while minimizing harm to healthy tissues.

What evidence suggests that XMT-1660 might be an effective treatment for breast cancer?

Research has shown that XMT-1660, also known as emiltatug ledadotin, yields promising results in treating breast cancer. Studies have found it to be generally well-tolerated with a unique safety profile. Early data indicates it works effectively, particularly for patients with triple-negative breast cancer, a type lacking three common receptors. This treatment may also benefit those who have already tried other therapies. Initial results suggest that XMT-1660 could meet a growing need in breast cancer care. ^{1 4 6 7 8}

Who Is on the Research Team?

Robert Burger, MD

Principal Investigator

Mersana Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors like ovarian, breast, endometrial, fallopian tube, or peritoneal cancer. They should be in good physical condition (ECOG 0-1), have at least one measurable tumor lesion and agree to a biopsy if safe. Not eligible if they've had another cancer treatment within 2 years (except some skin cancers or localized treatments), severe diseases that could affect the study's process, major surgery or anticancer therapy too close to the start of this study, untreated brain metastases, or prior specific ADC treatments.

Inclusion Criteria

I have had a brain MRI recently or will have one due to my triple-negative breast cancer or symptoms/history of brain metastases.

My cancer has returned or spread and didn't respond to treatment or I couldn't tolerate the treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a serious heart condition.

I have a history of serious liver conditions.

I do not have any severe illnesses that could worsen my condition or affect the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660

17 months

Dose Expansion

Use the dose found in the Dose Escalation phase to assess the safety and efficacy of XMT-1660 in treating solid tumor cancers

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• XMT-1660

Trial Overview The clinical trial is testing XMT-1660's effectiveness on participants with various types of solid tumors. The main focus is to see how well it works against these cancers and what effects it has on patients' bodies.

How Is the Trial Designed?

Group I: XMT-1660 Experimental Treatment 1 Intervention

Single arm XMT-1660 alone (monotherapy)

Who Is Running the Clinical Trial?

Mersana Therapeutics

Lead Sponsor

Trials

11

Recruited

1,500+

Published Research Related to This Trial

Bivatuzumab mertansine, a monoclonal antibody targeting CD44v6, showed potential efficacy in treating patients with incurable squamous cell carcinoma, but its development was halted due to significant skin toxicity, including a fatal case of toxic epidermal necrolysis in one patient.

The study involved seven patients receiving a total of 23 doses, revealing that while most skin reactions were reversible, the serious adverse events raised concerns about the safety profile, leading to the decision to discontinue further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Tijink, BM., Buter, J., de Bree, R., et al.[2022]

B7-H4 is highly expressed in various subtypes of breast cancer while showing low expression in normal tissues, making it a promising target for antibody-drug conjugates (ADCs) in cancer therapy.

The developed anti-B7-H4 TDC, which links a potent drug to an antibody, demonstrated significant tumor regression in models of triple-negative breast cancer, indicating its potential efficacy as a targeted treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-B7-H4 antibody-drug conjugate for the treatment of breast cancer. Leong, SR., Liang, WC., Wu, Y., et al.[2022]

The novel antibody-drug conjugate platform, Dolasynthen (DS), allows for precise optimization of drug-to-antibody ratios and site-specific conjugation, enhancing targeted drug delivery to tumors.

XMT-1660, an ADC developed using this platform targeting the B7-H4 protein, showed complete tumor regressions in various cancer models and has entered clinical development, indicating promising efficacy in treating cancers with high B7-H4 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer. Toader, D., Fessler, SP., Collins, SD., et al.[2023]

The DESTINY-Breast03 study, a phase III trial, compared trastuzumab emtansine and trastuzumab deruxtecan in patients with HER2+ metastatic breast cancer, revealing that trastuzumab deruxtecan significantly improved treatment efficacy.

Trastuzumab deruxtecan also demonstrated a better safety profile compared to trastuzumab emtansine, making it a promising option for patients with this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan Data Impresses at ESMO. [2022]

Sacituzumab govitecan (SG) is an effective antibody-drug conjugate for treating metastatic breast cancer, particularly in triple-negative and hormone receptor-positive types, significantly improving treatment outcomes.

However, SG therapy is associated with notable hematologic toxicities, such as neutropenia in up to 72% of patients, requiring careful management strategies like dose adjustments and prophylactic treatments to ensure patient safety and adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing adverse events of sacituzumab govitecan. Schlam, I., Tarantino, P., Tolaney, SM.[2023]

The METxMET-M114 antibody-drug conjugate (ADC) shows significant and lasting tumor regression in models of lung cancer with high MET expression, including those resistant to existing MET-targeted therapies.

In a toxicology study on cynomolgus monkeys, METxMET-M114 was well tolerated at effective doses, indicating its potential safety and efficacy for treating MET-overexpressing tumors in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade. DaSilva, JO., Yang, K., Surriga, O., et al.[2023]

Cantuzumab mertansine, administered at a recommended dose of 235 mg/m2 every 3 weeks, showed manageable safety with primarily acute and reversible liver enzyme elevations, along with common but mild side effects like nausea and fatigue.

In a study of 37 patients with CanAg-expressing solid tumors, there was preliminary evidence of antitumor activity, including minor regressions in some patients and stable disease in others, suggesting potential for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. Tolcher, AW., Ochoa, L., Hammond, LA., et al.[2016]

Antibody-drug conjugates (ADCs) are a promising new class of targeted therapies for metastatic breast cancer, designed to deliver chemotherapy more precisely and reduce toxicity compared to traditional chemotherapy.

The review highlights two recently FDA-approved ADCs, trastuzumab deruxtecan and sacituzumab govitecan, and discusses ongoing clinical trials that may significantly alter treatment strategies for both early and advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of New Antibody-Drug Conjugates in Breast Cancer: To Infinity and Beyond. Barroso-Sousa, R., Tolaney, SM.[2022]

Antibody-drug conjugates (ADCs) like trastuzumab deruxtecan and sacituzumab govitecan have shown promising activity in treating pretreated metastatic hormone receptor-positive (HR+) breast cancer, which traditionally relied on endocrine therapy.

Identifying which patients will benefit most from ADCs and managing their associated toxicities are now key challenges in integrating these treatments into the care of HR+ metastatic breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-Drug Conjugates in HR+ Breast Cancer: Where Are We Now and Where Are We Heading? De Santis, P., Sanna, V., Perrone, M., et al.[2023]

Citations

1. ir.mersana.com ir.mersana.com/news-releases/news-release-details/mersana-therapeutics-announces-positive-initial-clinical-data

Initiation of Expansion in Triple Negative Breast Cancer Emiltatug ledadotin observed to be generally well tolerated with differentiated safety and tolerability profile

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3009

Initial phase 1 dose escalation data for emiltatug ledadotin ... Based on the initial reported data, Emi-Le appears to have encouraging clinical activity and tolerability in a heavily pretreated population.

3. cancernetwork.com cancernetwork.com/view/xmt-1660-earns-fast-track-designation-for-her2-low-negative-breast-cancer

XMT-1660 Earns Fast Track Designation for HER2–Low/ ... The results indicate that [XMT-1660] may help address an already substantial and growing need among [patients with] topo-1–experienced breast ...

4. onclive.com onclive.com/view/emiltatug-ledadotin-generates-positive-initial-data-in-advanced-metastatic-solid-tumors

Emiltatug Ledadotin Generates Positive Initial Data in ... Emiltatug ledadotin produced positive initial phase 1 data in breast, ovarian, and endometrial cancer, as well as adenoid cystic carcinoma type 1.

5. esmoopen.com esmoopen.com/article/S2059-7029(25)00739-2/fulltext

298MO Clinical activity of emiltatug ledadotin (Emi-Le), a ... Emi-Le appears to have encouraging clinical activity and tolerability in a heavily pretreated TNBC population with high B7-H4 expression who had previously ...

6. onclive.com onclive.com/view/emiltatug-ledadotin-shows-early-clinical-activity-and-safety-in-advanced-metastatic-tnbc

Emiltatug Ledadotin Shows Early Clinical Activity and ... Patients with B7-H4–low TNBC who received 4 or fewer lines of therapy achieved a median OS of 5.7 months (95% CI, 3.2-NR). “There's a high unmet ...

7. dailyreporter.esmo.org dailyreporter.esmo.org/esmo-breast-cancer-2025/latest-news/promising-early-results-for-emiltatug-ledadotin-in-heavily-pretreated-triple-negative-breast-cancer

Promising early results for emiltatug ledadotin in heavily ... Phase 1 trial data highlights preliminary efficacy and manageable safety of B7-H4–targeted ADC in women receiving one prior topoisomerase-1 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985252/

B7 Homolog 4 (B7-H4)-Directed Agents in Oncology ... [10 ,11] In vivo, the ADC emiltatug ledadotin (XMT-1660) exhibited dose-dependent antitumor activity, with complete tumor regression observed in ...