Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors (ARCS-Multi)

Bayer

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Anetumab ravtansine (BAY94-9343); Drug: Cisplatin; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03102320

2016-004002-33 (EudraCT Number)

15834

Details and patient eligibility

About

The key purpose of the main part of the study is to assess efficacy and safety of anetumab ravtansine as monotherapy or combination therapy for mesothelin expressing advanced solid tumors.

The main purpose of the safety lead-in (dose-finding) part of the study is to determine the safety and tolerability of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine, and to determine the MTD of anetumab ravtansine in combination with cisplatin for mesothelin expressing advanced cholangiocarcinoma and in combination with gemcitabine for mesothelin expressing advanced adenocarcinoma of the pancreas.

Patients will receive anetumab ravtansine every three weeks in monotherapy for most indications. In cholangiocarinoma and adenocarinoma of the pancreas, 3-weekly anetumab ravtansine is administered in combination with cisplatin or gemcitabine respectively (both administered in a 2 week on / 1 week off schedule).

Treatment will continue until disease progression or until another criterion for withdrawal is met. .Efficacy will be measured by evaluating the tumor's objective response rate. Radiological tumor assessments will be performed at defined time points until the patient's disease progresses.

Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue will also be collected for mesothelin expression testing and biomarker analyses.

Enrollment: 173 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Availability of tumor tissue for mesothelin expression testing and for further biomarker analysis
• Histologically-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (or for thymic carcinoma, at least one measurable lesion per International Thymic Malignancy Interest Group (ITMIG) modified RECIST 1.1 criteria
• Adequate bone marrow, liver, renal and coagulation function
• Left ventricular ejection fraction (LVEF) ≥ 50% of the lower limit of normal (LLN) according to local institutional ranges
• Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion criteria

• Exposure to more than one prior anti-tubulin/microtubule agent
• Corneal epitheliopathy or any eye disorder that may predispose the patients to this condition
• Symptomatic Central nervous system (CNS) metastases and/or carcinomatous meningitis
• Contraindication to both CT and MRI contrast agents
• Active hepatitis B or C infection
• Pregnant or breast-feeding patients
• Tumor type specific exclusion criteria

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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173 participants in 3 patient groups

Cholangiocarcinoma

Experimental group

Description:

Safety lead-in phase will determine the MTD of anetumab ravtansine administered in combination with cisplatin. Please note the study is no longer recruiting for the cholangiocarcinoma safety lead-in phase. During the main study phase anetumab ravtansine will be administered at the determined MTD in combination with cisplatin. Please note the main study phase for cholangiocarcinoma will no longer be going ahead.

Treatment:

Drug: Anetumab ravtansine (BAY94-9343)

Drug: Cisplatin

Adenocarcinoma of the pancreas

Experimental group

Description:

Safety lead-in phase will determine the MTD of anetumab ravtansine administered in combination with gemcitabine During the main study phase, anetumab ravtansine will be administered at the determined MTD in combination with gemcitabine

Treatment:

Drug: Gemcitabine

Drug: Anetumab ravtansine (BAY94-9343)

Other solid tumors

Experimental group

Description:

(Non-small cell adenocarcinoma of the lung (NSCLC adenocarcinoma), Adenocarcinoma of the breast - triple negative (TNBC), Gastric adenocarcinoma including gastroesophageal junction (GEJ Cancer, Thymic carcinoma) During the main study phase, anetumab ravtansine will be administered at dose of 6.5 mg/kg in solid tumors

Treatment:

Drug: Anetumab ravtansine (BAY94-9343)