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Clinical Trial 20474

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03319628

Phase: Phase I
Principal Investigator: Saltos, Andreas

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients with Solid Tumors Likely to Express NaPi2b

Summary

This is a multi-center study of XMT-1536 in patients with tumors likely to express NaPi2b.

Objective

Primary in Dose Escalation (DES): Determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of XMT-1536 administered intravenously once every four weeks Assess the safety and tolerability of XMT-1536 Primary in Expansion (EXP): Assess further the safety and tolerability of XMT-1536 administered at the MTD/RP2D identified in the DES Assess the preliminary anti-neoplastic activity of XMT-1536 Secondary in DES: Assess the preliminary anti-neoplastic activity of XMT-1536 Secondary in DES and EXP: Assess the pharmacokinetics (PK) of XMT-1536, its release product, and selected metabolites Assess the development of anti-drug antibodies to XMT-1536 Assess the association of tumor expression of NaPi2b and objective tumor response to XMT-1536 Assess safety and efficacy in ovarian cancer subpopulations, including patients previously treated and failed therapy with bevacizumab and patients with and without BRCA mutation who were previously treated and failed therapy with PARP inhibitors Exploratory in DES and EXP: Retrospectively evaluate the association of objective response with tumor expression of genes other than NaPi2b, or other tumor molecular and histologic features

Treatments

Therapies

Immunotherapy

Medications

XMT-1536 ()

Inclusion Criteria

Ability to give informed consent.

ECOG performance status 0 or 1.

Measurable disease as per RECIST, version 1.1.

Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade 1 or less except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on less than or equal to 10 mg daily prednisolone (or equivalent) chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy

Caridac left ventricular ejection fraction (LVEG) greater than or equal to 50% or the lower than the institution's lower limit of normal by either Echo or MUGA scan.

Adequate organ function.

During the study, female study participants of child-bearing potential must use a highly effective non-hormonal form of contraception for the duration of study drug administration and for at least 6 months after the last dose of study drug. Examples of non-hormonal highly effective contraceptive methods include: a. intrauterine device (IUD) b. bilateral tubal occlusion c. vasectomized partner d. female sterilization. e. sexual abstinence Sexual Abstinence is defined by refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence shall be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the study patient. Note: Periodic abstinence (calendar, symptom-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Male study participants must use barrier contraception (condoms) for the duration of study drug and for at least 6 months after the last dose of study drug. The WOCBP partners of male study participants must use highly effective contraception for the duration of study drug and for at least 6 months after the last dose of study drug.

Histologically or cytologically confirmed solid tumors of the types specified below, with incurable, locally advanced or metastatic disease that has failed standard therapy or for which no standard treatment option exists.

Other criteria may apply

Exclusion Criteria

Major surgery within 28 days of starting study treatment or systemic anti-cancer therapy within the lesser 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); or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity (consultation with the Sponsor Medical Monitor is recommended).

Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis. Patients are eligible if CNS metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to enrollment. In addition, patients must be either off corticosteroids, or on a stable/decreasing dose of less than or equal to 10 mg daily prednisone (or equivalent). Anticonvulsants are allowed except for those drugs associated with liver toxicity.

Untreated, known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). In addition, negative serology is required during screening (baseline) for HBV and HCV is required at baseline for HBV and HCV: HBV: Patients with serologic evidence of chronic HBV infection should have an HBV viral load below the limit of quantification to be eligible. HCV: Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load below the limit of quantification. HIV: Screening for HIV is not required except if mandated by local regulations.

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, patients are excluded with the following characteristics: (a) A marked baseline prolongation of QT/QTc interval (b) A history of additional risk factors for Torsade's de Pointes (c) The use of concomitant medications that prolong the QT/QTc interval will be reviewed first with the Sponsor Medical Monitor.

History of cirrhosis, hepatic fibrosis, varices, or other clinically significant liver disease. FibroScan testing may be required for patients with a history of chronic liver disease, e.g., fatty liver.

Patients cannot receive drugs associated with hepatotoxicity concurrent with XMT-1536 administration. Patients may receive acetaminophen/paracetamol for a limited time but at a total daily dose of less than or equal to 2 g per day. Use of NSAIDs or steroids for treatment of fever is encouraged.

Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

Currently active pneumonitis or interstitial lung disease or a history of Grade 2 2 pneumonitis within the last 2 months that required medical intervention such as treatment with corticosteroids.

Pregnant or nursing women.

Diagnosis of additional malignancy that progressed or required active treatment within the last 2 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix

Active corneal disease, or history of corneal disease within 12 months prior to enrollment.

Use of strong CYP450 inhibitors.

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