A Study of XMT-1660 in Participants With Solid Tumors

Study Overview
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Brief Summary
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A Study of XMT-1660 in Solid Tumors

Detailed Description
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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.

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

Conditions
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Triple Negative Breast Cancer, Breast Cancer, Endometrial Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: XMT-1660


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has proven 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 Participant must have at least one measurable lesion(s) as defined by RECIST version 1.1. Participant must be willing to undergo a minimally invasive tumor biopsy to obtain tumor tissue for local testing, if medically feasible, prior to C1D1. If the investigator feels a biopsy is not medically feasible, an exemption request must be submitted to the study Medical Monitor for approval. Exclusion Criteria: Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin or maytansinoid 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. Participant has current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations. Further, participants are excluded with the following characteristics: Participant has untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis. Participants are eligible if CNS metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XMT-1660<br>Single arm XMT-1660 alone (monotherapy) | Drug: XMT-1660<br>* XMT-1660 will be administered through a vein in your arm or port catheter (intravenously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation) | Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660 | 17 months | 
| Incidence of adverse events (Dose Escalation and Dose Expansion) | 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 | 3 years | 
| Objective Response Rate (ORR) (Dose Expansion) | 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 | approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) (Dose Escalation) | 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 | Up to approximately 3 years | 
| Duration of response (DOR) (Dose Escalation and Dose Expansion) | The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response | Up to approximately 3 years | 
| Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 | 3 years | 
| Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 | 3 years | 
| Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 | 3 years | 
| Systemic clearance of XMT-1660 (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 by measuring the rate at which the drug is eliminated from the body | 3 years | 
| Apparent terminal elimination half-life of XMT-1660 (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 | 3 years | 
| Volume of Distribution (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 | 3 years | 
| Trough concentration of XMT-1660 (Ctrough) (Dose Expansion) | Assess the pharmacokinetics of XMT-1660 by measuring the lowest concentration of drug before dosing | 3 years | 
| Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion) | Assess the development of antidrug antibodies (ADA) and neutralizing antibodies (nAb) to XMT-1660 | 3 years |