XMT-1660 for Breast Cancer

Recruiting at 20 trial locations

Overseen By Caroline Rogalski

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Mersana Therapeutics

Must not be taking: Auristatin ADCs

Disqualifiers: Untreated CNS metastases, Cirrhosis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called XMT-1660 to see if it is safe and what side effects it might have. It focuses on patients whose cancer has come back, spread locally, or spread throughout the body. The study will first find a safe dose and then check if this dose helps treat solid tumors.

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.

What data supports the effectiveness of the drug XMT-1660 for breast cancer?

Research shows that XMT-1660, a drug designed to target a protein called B7-H4, has been effective in causing complete tumor regressions in breast cancer models. It works by delivering a powerful cancer-killing agent directly to the cancer cells, and its effectiveness is linked to the presence of B7-H4 in the tumors. ^{1 2 3 4 5}

What safety data exists for XMT-1660 in humans?

XMT-1660, a B7-H4-targeted antibody-drug conjugate, has entered clinical development in a phase I study to assess its safety in humans. Preclinical studies showed it caused complete tumor regressions in models of breast cancer, and its safety profile is being evaluated in ongoing trials. ^{1 2 6 7 8}

What makes the drug XMT-1660 unique for treating breast cancer?

XMT-1660 is unique because it is an antibody-drug conjugate (ADC) that specifically targets the B7-H4 protein, which is overexpressed in certain breast cancers. This allows for targeted delivery of the drug to cancer cells, potentially leading to better outcomes and fewer side effects compared to non-targeted therapies. ^{1 2 6 7 9}

Research Team

Robert Burger, MD

Principal Investigator

Mersana Therapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• XMT-1660 (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

An anti-B7-H4 antibody-drug conjugate for the treatment of breast cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical Development of New Antibody-Drug Conjugates in Breast Cancer: To Infinity and Beyond. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Managing adverse events of sacituzumab govitecan. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Antibody-Drug Conjugates in HR+ Breast Cancer: Where Are We Now and Where Are We Heading? [2023]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan Data Impresses at ESMO. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade. [2023]