Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin E

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

https://clinicaltrials.gov/ct2/show/NCT03102320

Purpose
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 cholangiocarcinoma 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 may also be collected for review and biomarkers.

Condition Intervention Phase
Neoplasms
Drug: Cisplatin
Drug: Gemcitabine
Drug: Anetumab ravtansine (BAY94-9343)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:
Maximum tolerated dose (MTD) of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine in patients with mesothelin-expressing cholangiocarcinoma and pancreatic adenocarcinoma [ Time Frame: At least 3 weeks after the last patient starts treatment ]
The highest dose of anetumab ravtansine that can be given so that not more than 1 out of 6 patients experiences a DLT (during the DLT evaluation period) will be declared as the MTD for anetumab ravtansine in combination with cisplatin or with gemcitabine

Objective response rate (ORR) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors [ Time Frame: 18 weeks after last patient starts treatment ]
A patient is a responder if the patient has a tumor response of CR or PR, as determined per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma). In the Phase 1b portion of this study, the ORR is defined separately in each indication and mesothelin expression cohort, as the number of responders divided by the number of treated patients in the indication and mesothelin expression cohort

Secondary Outcome Measures:
Number of serious and non-serious adverse events (AEs) [ Time Frame: 18 weeks after last patient starts treatment ]
Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.

Disease control rate (DCR) [ Time Frame: 18 weeks after last patient starts treatment ]
The DCR is defined as the number of patients with disease control divided by the number of treated patients.

Duration of response (DOR) [ Time Frame: Approximately 24 months after last patient starts treatment ]
DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death

Durable response rate (DRR) [ Time Frame: Approximately 24 months after last patient starts treatment ]
A durable responder is defined as a responder (CR or PR) with a duration of response per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma) of 180 days or more. The DRR is the number of durable responders divided by the number of treated patients.

Progression free survival (PFS) [ Time Frame: Approximately 24 months after last patient starts treatment ]
PFS is defined as time from start of treatment until disease progression according to RECIST 1.1 (ITMIG modified RECIST 1.1 criteria for thymic carcinoma) or death.

Estimated Enrollment: 348
Anticipated Study Start Date: July 31, 2017
Estimated Study Completion Date: February 11, 2020
Estimated Primary Completion Date: May 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cholangiocarcinoma
Safety lead-in phase will determine the MTD of anetumab ravtansine administered in combination with cisplatin During the main study phase anetumab ravtansine will be administered at the determined MTD in combination with cisplatin
Drug: Cisplatin
Cisplatin 25 mg/m2 IV administered on day 1 and day 8 of 21 day cycle, for up to maximum 6 cycles
Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered
Experimental: Adenocarcinoma of the pancreas
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
Drug: Gemcitabine
Gemcitabine 1000 mg/m2 IV administered on days 1 and 8 of a 21-day cycle
Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered
Experimental: Other solid tumors
(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
Drug: Anetumab ravtansine (BAY94-9343)
Anetumab ravtansine 6.5mg/kg IV in monotherapy indications. For combination indications, the MTD determined in safety lead in phase will be administered

Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Availability of tumor tissue for mesothelin expression testing
Histologically-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
At least one measurable lesion according to either Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or International Thymic Malignancy Interest Group (ITMIG) modified RECIST 1.1 as applicable
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:

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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03102320

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options ‘3’ or ‘4’) (+)1-888-84 22937

Show 57 Study Locations
Sponsors and Collaborators
Bayer
More Information

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03102320 History of Changes
Other Study ID Numbers: 15834
2016-004002-33 ( EudraCT Number )
Study First Received: March 30, 2017
Last Updated: April 5, 2017
Individual Participant Data
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
cholangiocarcinoma
pancreatic cancer
triple-negative breast cancer
non-small cell lung cancer
thymic carcinoma
gastric including gastroesophageal junction cancer

Additional relevant MeSH terms:
Gemcitabine
Cisplatin
Maytansine
Immunoconjugates
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on April 07, 2017