A Study of XMT-1660 in Participants With Solid Tumors

• ClinicalTrials.gov Identifier: NCT05377996
• Recruitment Status: Recruiting
• First Posted: May 17, 2022
• Last Update Posted: March 20, 2024
• Sponsor: Mersana Therapeutics
• Information provided by (Responsible Party): Mersana Therapeutics

Tracking Information

• First Submitted Date: May 2, 2022
• First Posted Date: May 17, 2022
• Last Update Posted Date: March 20, 2024
• Actual Study Start Date: August 15, 2022
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2023)

• Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation) [ Time Frame: 17 months ]
  Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660
• Incidence of adverse events (Dose Escalation and Dose Expansion) [ Time Frame: 3 years ]
  Assess the safety and tolerability of XMT-1660 by determining the number of patients with adverse events from date of first dose to 30 days post last dose
• Objective Response Rate (ORR) (Dose Expansion) [ Time Frame: approximately 3 years ]
  The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Original Primary Outcome Measures (submitted: May 11, 2022)

• Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation) [ Time Frame: 17 months ]
  Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of XMT-1660
• Incidence of adverse events (Dose Escalation and Dose Expansion) [ Time Frame: 3 years ]
  Assess the safety and tolerability of XMT-1660 by determining the number of patients with adverse events from date of first dose to 30 days post last dose
• Objective Response Rate (ORR) (Dose Expansion) [ Time Frame: approximately 3 years ]
  The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Duration of response (DOR) (Dose Expansion) [ Time Frame: approximately 3 years ]
  The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response

Current Secondary Outcome Measures (submitted: February 17, 2023)

• Objective Response Rate (ORR) (Dose Escalation) [ Time Frame: Up to approximately 3 years ]
  The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Duration of response (DOR) (Dose Escalation and Dose Expansion) [ Time Frame: Up to approximately 3 years ]
  The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response
• Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Systemic clearance of XMT-1660 (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660 by measuring the rate at which the drug is eliminated from the body
• Apparent terminal elimination half-life of XMT-1660 (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Volume of Distribution (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Trough concentration of XMT-1660 (Ctrough) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660 by measuring the lowest concentration of drug before dosing
• Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion) [ Time Frame: 3 years ]
  Assess the development of antidrug antibodies (ADA) and neutralizing antibodies (nAb) to XMT-1660

Original Secondary Outcome Measures (submitted: May 11, 2022)

• Objective Response Rate (ORR) (Dose Escalation) [ Time Frame: Up to approximately 3 years ]
  The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Duration of response (DOR) (Dose Escalation) [ Time Frame: Up to approximately 3 years ]
  The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response
• Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Systemic clearance of XMT-1660 (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660 by measuring the rate at which the drug is eliminated from the body
• Apparent terminal elimination half-life of XMT-1660 (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Volume of Distribution (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660
• Trough concentration of XMT-1660 (Ctrough) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the pharmacokinetics of XMT-1660 by measuring the lowest concentration of drug before dosing
• Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Expansion) [ Time Frame: 3 years ]
  Assess the development of antidrug antibodies (ADA) and neutralizing antibodies (nAb) to XMT-1660

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of XMT-1660 in Participants With Solid Tumors
• Official Title: A Phase 1, First-in-human, Dose Escalation and Expansion, Multicenter Study of XMT-1660 in Participants With Solid Tumors
• Brief Summary: A Study of XMT-1660 in Solid Tumors

Detailed Description

This first-in-human (FIH) study will test the safety and side effects of a drug called XMT-1660. A side effect is anything a drug does to the body besides treating the disease.

Participants in the study will have cancer that has come back after a period of time during which the cancer could not be detected (recurrent), spread in the body near where it started (advanced) or spread through the body (metastatic).

The study will have two parts. The first part called Dose Escalation will find out how much XMT-1660 should be given to participants. The second part called Dose Expansion will use the dose found in the first part to find out how safe XMT-1660 is and if it works to treat solid tumor cancers.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Triple Negative Breast Cancer
• Breast Cancer
• Endometrial Cancer
• Ovarian Cancer
• Fallopian Tube Cancer
• Primary Peritoneal Cavity Cancer
• Adenoid Cystic Carcinoma

Intervention

Drug: XMT-1660

XMT-1660 will be administered through a vein in your arm or port catheter (intravenously)

Study Arms

Experimental: XMT-1660

Single arm XMT-1660 alone (monotherapy)

Intervention: Drug: XMT-1660

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 21, 2024): 319
• Original Estimated Enrollment (submitted: May 11, 2022): 166
• Estimated Study Completion Date: May 2027
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Recurrent or advanced solid tumor and has disease progression after treatment with available anti-cancer therapies known to confer benefit or is intolerant to treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• At least one measurable lesion(s) as defined by RECIST version 1.1.
• Tumor tissue, either archival or from a fresh tumor biopsy, available for testing or be willing to undergo a minimally invasive tumor biopsy to obtain tumor tissue for local testing, if not medically contraindicated, prior to Cycle 1 Day 1

• Brain magnetic resonance imaging (MRI) during the Pre- Screening/Screening period unless obtained within 30 days prior to enrollment (based on standard clinical care), if they meet either of the following criteria:

  1. All participants with TNBC
  2. Participants with a history of brain metastases or with neurologic symptoms or signs suspicious for brain metastases.

Exclusion Criteria:

• Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin payload. Prior treatment with another ADC containing other payloads is allowed.
• Major surgery within 28 days of starting study treatment, systemic anticancer therapy within the time period of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), whichever is less, or palliative radiation therapy within 14 days of starting study treatment.
• Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.

• Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.

  1. Participants are eligible if CNS metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment.
  2. In addition, participants must be either off corticosteroids, or on a stable/decreasing dose of ≤ 10 mg daily prednisone (or equivalent). Anticonvulsants are allowed except for those drugs associated with liver toxicity
  3. Participants may be eligible if CNS lesions are asymptomatic, equivocal for metastases or do not require specific therapy in the opinion of the investigator
• Prior B7-H4 targeted treatment.
• History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases.
• Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could increase the risk of serious adverse events (SAEs) or interfere with per-protocol evaluations, in the judgment of either the Sponsor or the Investigator.
• Clinically significant cardiovascular disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Caroline Rogalski; 1-617-715-8214; medicalinformation@mersana.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05377996
• Other Study ID Numbers: MER-XMT-1660-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Mersana Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Mersana Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Robert Burger, MD; Mersana Therapeutics

• PRS Account: Mersana Therapeutics
• Verification Date: March 2024