Clinical Trial 18825

Cancer Type: Multiple
Interventions:XMT-1522

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Hatem Soliman

Overview

Study Title

A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1522 in Patients with Advanced Breast Cancer and Other Advanced Tumors Expressing HER2

Summary

The purposes of the first part of this study are: To find the highest dose of XMT-1522 that can be tolerated and seems reasonably safe; To gather information on how participants react to receiving XMT-1522; To evaluate how long XMT-1522 stays in the blood, at what level and what changes, if any, XMT-1522 causes. For example, does the participant's body develop proteins that work against the XMT-1522 or does their tumor change in size after receiving XMT-1522?

Objective

1 PRIMARY OBJECTIVES: Dose Escalation (DES): 1.1. Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1522 administered intravenously once every three weeks. 1.2. Assess the safety and tolerability of XMT-1522. Expansion (EXP): 1.3. Assess further the safety and tolerability of XMT-1522 administered at the MTD/RP2D identified in the DES. 1.4. Assess the preliminary anti-neoplastic activity of XMT-1522. 2 SECONDARY OBJECTIVES: DES and EXP: 2.1. Assess the pharmacokinetics (PK) of XMT-1522, its release product, and selected metabolites. 2.2. Assess the development of anti-drug antibodies to XMT-1522. DES Only: 2.3. Assess the preliminary anti-neoplastic activity of XMT-1522. 3 EXPLORATORY OBJECTIVE: 3.1. Retrospectively evaluate the association of objective response and alternative assays for measurement of HER2 expression.

Inclusion Criteria

  • Able and willing to give informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Measurable disease via RECIST
  • Resolution of all toxic side effects from prior oncology treatments
  • Adequate organ function as measured by various blood parameters
  • Not pregnant or lactating, willing to prevent pregnancy while on study and for 6 months after the last dose of XMT-1522
  • Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 1+ or 2+ - OR - Histologically or cytologically confirmed adenocarcinoma of the breast with unresectable locally advanced disease, or metastatic disease and HER2 IHC 3+ or positive for HER2 gene amplification
  • Progressed following all standard of care therapies for advanced breast cancer - OR - Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and HER2 IHC 3+ or positive for HER2 gene amplification - OR - Histologically or cytologically confirmed Stage IIIb or IV non-small cell lung cancer HER2 IHC 2+ or 3+ by local laboratory assessment.

  • Exclusion Criteria

  • Major surgery, radiation therapy, or systemic anti-cancer therapy within 28 days of starting study treatment.
  • Some types of brain metastases
  • Peripheral neuropathy of Grade 2 within 3 weeks prior to the first study therapy
  • History of exposure to cumulative doxorubicin dose ≥ 360 mg/meter squared. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/meter squared of doxorubicin
  • History of clinically significant cardiac dysfunction
  • Current known active infection with HIV, hepatitis B virus, or hepatitis C virus
  • Current severe, uncontrolled systemic disease
  • Severe dyspnea at rest, due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
  • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome
  • Patients who participate in the dose escalation segment of the study cannot participate in the expansion segment of the study.