A dose escalation and expansion study of XMT-1536 en patients with solid tumors.

Phase 1

• Conditions: High grade serous ovarian cancer or non-small cell lung cancer (NSCLC), adenocarcinoma subtype; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000630-17-NO
• Lead Sponsor: Mersana Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-30
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 422

Inclusion Criteria

For Dose Escalation, Expansion and Uplift
1.Females and males, aged =18 years old
2.ECOG performance status 0 or 1
3.Measurable disease as per RECIST, version 1.1
4.Resolution of all acute toxic effects of prior therapy or surgical procedures to =Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on =10 mg daily [prednisolone] (or equivalent) chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
5.Cardiac left ventricular ejection fraction (LVEF) =50% or = the institution's lower limit of normal by either Echo or MUGA scan
6. Adequate organ function as defined by the following criteria:
a. Absolute neutrophil count (ANC) =1500 cells/mm3
b. Platelet count =100,000/mm3
c. Hemoglobin =9 g/dLa
d. In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institutional upper limit of normal (ULN) in the absence of any other indicator of liver dysfunction. Patients on anticoagulants are allowed if their relevant laboratory values are within the therapeutic window.
e. Estimated glomerular filtration rate (GFR) =45 mL/min
f. Total bilirubin =ULN
Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia may be eligible after discussion with the Sponsor Medical Monitor.
7. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) =1.5 times the institutional ULN.
8. Albumin =3.0 g/dL
9. Female 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.
Please see Appendix 7 of the Protocol for examples of non-hormonal highly effective contraceptive methods.
10.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 (Appendix 7.).
11. Able to provide informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 211
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 211

Exclusion Criteria

For Dose Escalation, Expansion and Uplift
1. Major surgery within 28 days of starting study treatment, 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).
2. Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
a. Patients are eligible if CNS metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to enrollment.
b. In addition, patients 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. 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:
a. HBV: Patients with serologic evidence of chronic HBV infection should have an HBV viral load below the limit of quantification to be eligible.
b. HCV: Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load below the limit of quantification.
c. HIV: screening for HIV is not required except if mandated by local regulations or indicated based on clinical assessment.
4. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could risk of adverse events, whether or not potentially related to study treatment (in unclear cases, consultation with the Medical Monitor is recommended). Further, patients are excluded with the following characteristics:
a. A marked baseline prolongation of QT/QTcQTcF interval >CTCAE G1: repeated demonstration of a QTcF interval >480 milliseconds (ms) using Frederica's QT correction formula.
b. A history of additional risk factors for Torsade's de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
5. History of cirrhosis, hepatic fibrosis, esophageal or gastric 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. Testing beyond laboratory studies otherwise defined in the eligibility criteria, to diagnose potentially clinically significant liver disease based on risk factors such as hepatic steatosis or history of excessive alcohol intake, will be based on clinical judgement of the investigator.
6. 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 =2 g per day. Use of NSAIDs or steroids for treatment of fever is encouraged.
7. Current use of either constant or intermittent supplementary oxygen therapy.
8. History of or suspected pneumonitis, or interstitial lung disease
9. Oxygen saturation on room air <93%.
10. Pregnant or nursing women
11.Diagnosis of additional malignancy that progressed or required active treatment within at least 2 years , except for adequately treated basal cell or squamous cell skin cancer, or carcinoma

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified