Phase I Study of Anetumab Ravtansine in Hepatic or Renal Impairment

Bayer

Status and phase

Completed

Phase 1

Conditions

Neoplasms

Treatments

Drug: Anetumab ravtansine (BAY94-9343)

Study type

Interventional

Funder types

Industry

Identifiers

NCT02696642

18327

2015-003897-33 (EudraCT Number)

Details and patient eligibility

About

To characterize the safety, tolerability, pharmacokinetics and immunogenicity of anetumab ravtansine in subjects with advanced solid cancers and with different degrees of hepatic or renal impairment

Enrollment

54 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female subjects aged ≥18 years
Histologically or cytologically confirmed, locally advanced or metastatic solid cancers known to express mesothelin on the tumor cell surface (e.g. predominantly epithelial [>=50% tumor component] pleural or peritoneal mesothelioma, epithelial ovarian cancer [including the fallopian tube or primary peritoneal], adenocarcinoma of the pancreas, triple-negative adenocarcinoma of the breast, non-small-cell adenocarcinoma of the lung, endometrial cancer, serous uterine cancer, gastric cancer [including the gastro-esophageal junction], colon cancer, cholangiocarcinoma, thymic carcinoma, etc.). Subjects with resected primary cancers who have documented metastases or local recurrence are eligible.
Subjects must have no standard therapy available, or have actively refused standard therapy
Subjects must meet the criteria for one of the 4 treatment groups:
- Group A: Adequate hepatic and renal function (controls)
- Group B: Mild hepatic impairment, i.e. Grade A according to the Child-Pugh Classification (total score of 5 or 6) and adequate renal function
- Group C: Moderate hepatic impairment, i.e. Grade B according to the Child-Pugh Classification (total score of 7, 8 or 9) and adequate renal function
- Group D: Moderate renal impairment, i.e. eGFR (estimated glomerular filtration rate) <60 and ≥30 mL/min per 1.73 m*2 and hepatic function better than, or equal to mild impairment according to the Child-Pugh Classification (total score ≤6)
Adequate bone marrow function
Life expectancy of at least 12 weeks
ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 (control and mild hepatic impairment groups), or 0-2 (moderate hepatic impairment and moderate renal impairment groups)

Exclusion criteria

Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except cervical carcinoma in situ, treated basal cell carcinoma, superficial noninvasive bladder tumors or any previous cancer curatively treated >3 years before the start of anetumab ravtansine
Subjects who have new or progressive brain or meningeal or spinal metastases
Subjects who have Gilbert's syndrome or other benign congenital hyperbilirubinemia are not eligible for the mild or moderate hepatic impairment or moderate renal impairment groups.
Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage/bleeding event of CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 bleeding within 4 weeks before the start of anetumab ravtansine
Subjects who have a history or current evidence of uncontrolled cardiovascular disease or hypertension.
Fridericia-corrected QT interval (QTcF) >480 ms, heart rate ≥100 beats per minute (bpm) or ≤45 bpm, LVEF (left ventricular ejection fraction) <50%
Subjects with corneal epitheliopathy or any eye disorder that may predispose the subjects to drug-induced corneal epitheliopathy or may interfere with diagnosis of treatment-emergent corneal epitheliopathy at the investigator's discretion in consultation with an ophthalmologist.
Subjects who have received systemic anticancer therapy (except pemetrexed, cisplatin, carboplatin and topical or intracavitary treatments with negligible absorption in systemic circulation ) within 4 weeks before the start of anetumab ravtansine, or within 5 half-lives of the anticancer agent before the start of anetumab ravtansine, whichever is longer. Mitomycin C or nitrosoureas must be excluded within 6 weeks before the start of anetumab ravtansine.
Subjects who have received radiotherapy within 4 weeks before the start of anetumab ravtansine
Use of drugs that, in the opinion of the investigator, have a strong potential for renal or hepatic toxicity within 2 weeks before the start of anetumab ravtansine until the EoT visit.
Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 2 weeks before the start of anetumab ravtansine until the EoT visit
Women who are pregnant or breast-feeding

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

54 participants in 4 patient groups

Control group

Experimental group

Description:

Anetumab ravtansine was given at 6.5 mg/kg body weight (BW) as a 1 hour intravenous (IV) infusion once every 3 weeks (Q3W) for subjects with adequate hepatic and renal function.

Treatment:

Drug: Anetumab ravtansine (BAY94-9343)

mild HI group

Experimental group

Description:

Anetumab ravtansine was given at 6.5 mg/kg BW as a 1 hour IV infusion Q3W for subjects with mild hepatic impairment (HI).

Treatment:

Drug: Anetumab ravtansine (BAY94-9343)

moderate HI group

Experimental group

Description:

Anetumab ravtansine was given at 6.5 mg/kg BW as a 1 hour IV infusion Q3W for subjects with moderate hepatic impairment (HI).