XMT-2056 for Breast Cancer

Recruiting at 15 trial locations

Overseen By June Buchanan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mersana Therapeutics

Must not be taking: Immunosuppressants, STING pathway drugs

Disqualifiers: Untreated CNS metastases, Recent malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

162 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-2056 for individuals with breast cancer that has returned or spread and shows the HER2 protein. The goal is to determine if XMT-2056 can slow or stop the cancer's growth. This study targets those whose cancer has progressed after other treatments or who cannot undergo standard therapies. Participants must have HER2-positive cancer confirmed by recent testing and be able to provide tumor samples. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking immunosuppressive medications at doses greater than 10 mg/day of prednisone (a type of steroid) or equivalent for at least 2 weeks before starting the study treatment. However, physiologic hormone replacement therapy is allowed.

Is there any evidence suggesting that XMT-2056 is likely to be safe for humans?

Research shows that XMT-2056 remains in the early testing phase, so limited safety information is available. Earlier studies indicated that XMT-2056 worked well against cancer cells, particularly in HER2-positive tumors. However, serious safety concerns have arisen. Recently, a study paused due to a participant experiencing a severe side effect. This suggests that while the treatment might be effective, it could also pose risks. As the treatment undergoes early trials, further research is necessary to fully understand its safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which usually involve chemotherapy, hormone therapy, or targeted therapy, XMT-2056 offers a new approach by utilizing a novel mechanism of action. Researchers are excited about XMT-2056 because it is designed to target specific cancer pathways with precision, potentially leading to more effective treatment outcomes and fewer side effects. This targeted approach may provide a new avenue for patients who don't respond well to existing therapies or have developed resistance, making it a promising addition to the current breast cancer treatment landscape.

What evidence suggests that XMT-2056 might be an effective treatment for breast cancer?

Research shows that XMT-2056, the investigational treatment in this trial, is a promising option for breast cancer, particularly for tumors with the HER2 protein, often present in more aggressive cases. Studies have demonstrated that XMT-2056 effectively fights tumors independently, even in cancers with varying HER2 levels. Notably, it outperforms a similar drug known as a free STING agonist and causes less inflammation as a side effect. Early tests also indicate that it can kill cancer cells even with low HER2 amounts. This evidence suggests that XMT-2056 could be a viable option for treating breast cancer, especially when other treatments might not be as effective. ^{1 2 3 6 7}

Who Is on the Research Team?

Brad Sumrow, MD

Principal Investigator

Mersana Therapeutics

Are You a Good Fit for This Trial?

This trial is for people with advanced or recurrent solid tumors that are HER2 positive, who've seen their cancer progress after treatment, can't tolerate current treatments, or have no other beneficial anti-cancer therapies available. Participants need to be in good physical condition (ECOG status 0-1) and have measurable disease. They must provide a fresh tumor biopsy unless medically unfeasible.

Inclusion Criteria

My cancer has returned or spread, is HER2 positive, and doesn't respond well to current treatments.

I can provide a recent tumor sample or, if not possible, an older sample with approval.

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

Exclusion Criteria

I am on high-dose immunosuppressants that can't be stopped for the study.

I haven't had active treatment for another cancer, except skin or certain breast/cervix cancers, in the last 2 years.

I have brain metastases but am stable and not on high doses of steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

The dose-finding portion of the study to assess the safety and tolerability of XMT-2056 and determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

15 months

Dose Expansion

Participants receive XMT-2056 to further assess safety, tolerability, and preliminary anti-tumor effect at the RP2D

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• XMT-2056

Trial Overview The study is testing XMT-2056 on patients with various types of cancers like breast, gastric, lung, and colorectal cancer that express the HER2 protein. The goal is to see how effective this new drug is on these specific tumors.

How Is the Trial Designed?

Group I: XMT-2056 Experimental Treatment 1 Intervention

XMT-2056 alone (monotherapy)

XMT-2056 is already approved in United States for the following indications:

Approved in United States as XMT-2056 for:

• Gastric cancer (orphan drug designation)

Who Is Running the Clinical Trial?

Mersana Therapeutics

Lead Sponsor

Trials

11

Recruited

1,500+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12010966/

XMT-2056, a HER2-Directed STING Agonist Antibody ... Notably, XMT-2056 demonstrated superior efficacy and reduced systemic inflammation compared with a free STING agonist. XMT-2056 exhibited concomitant immune- ...

2. ir.mersana.com ir.mersana.com/news-releases/news-release-details/mersana-therapeutics-present-preclinical-data-xmt-1660-xmt-2056

Mersana Therapeutics to Present Preclinical Data on XMT- ... The preclinical data presented show that XMT-2056 demonstrates robust anti-tumor activity as a monotherapy in both HER2-high and HER2-low ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05514717

A Study of XMT-2056 in Advanced/Recurrent Solid Tumors ... The first-in-human (FIH) study of XMT-2056 is a Phase 1, open-label study of XMT-2056 in previously treated patients with advanced/recurrent solid tumors ...

4. mersana.com mersana.com/wp-content/uploads/2022/04/AACR-2022_XMT-2056_Poster_Final.pdf

XMT-2056, a HER2-targeted Immunosynthen STING- ... XMT-2056 in combination with trastuzumab deruxtecan demonstrates improved activity in a trastuzumab resistant breast cancer model. XMT-2056 and trastuzumab ...

5. jitc.bmj.com jitc.bmj.com/content/12/suppl_2/a1173

1053 XMT-2056, a HER2-targeted immunosynthen STING ... We demonstrate that XMT-2056 effectively induces cytokine production and cancer cell-killing in PBMC co-cultures with cancer cells that express very low levels ...

6. targetedonc.com targetedonc.com/view/fda-halts-phase-1-trial-of-xmt-2056-for-her2-recurrent-metastatic-solid-tumors

FDA Halts Phase 1 Trial of XMT-2056 for HER2+ Recurrent ... The FDA has placed a clinical hold on the phase 1 trial (NCT05514717) of XMT-2056 following a report of a patient who experienced a recent grade 5 serious ...

7. ir.mersana.com ir.mersana.com/node/12106/pdf

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