Clinical trial NCT03102320: Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors
Official title: Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: cholangiocarcinoma
pancreatic cancer
triple-negative breast cancer
non-small cell lung cancer
thymic carcinoma
gastric including gastroesophageal junction cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: ImmunoGen, Inc.
name: MorphoSys AG
First posted: 2017-04-05
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients in the safety lead-in (SLI) phase who completed Cycle 1 or had a DLT and were not replaced.
timeFrame: At least 3 weeks after the last patient starts treatment
measure: Objective response (qualitative improvement from baseline) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors
timeFrame: Up to approximately 26 months after patient starts treatment
measure: Durable disease control (lack of progression from baseline) of anetumab ravtansine in indications pancreatic and gastric cancer (co-primary endpoint)
timeFrame: Up to approximately 26 months after patient starts treatment
Secondary outcomes:
measure: Number of serious and non-serious adverse events (AEs)
timeFrame: Approximately 26 months (Until 30 days after the last day of study treatment, or until later resolution of adverse events or determination by the investigator that the event will not improve)
measure: Disease control rate (DCR)
timeFrame: Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
measure: Duration of response (DOR)
timeFrame: Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
measure: Durable response rate (DRR)
timeFrame: Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
measure: Progression free survival (PFS)
timeFrame: Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
measure: Durable disease control rate (DDCR) of anetumab ravtansine in indications other than pancreatic and gastric cancer
timeFrame: Up to approximately 24 months after last patient starts treatment, or until earlier disease progression [assessed every 6 weeks for the first 6 months, every 9 weeks until end of year 1 and every 12 weeks thereafter]
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Medical Center - New Orleans
state: Louisiana
city: Bethesda
country: United States
facility: National Cancer Institute - Maryland
state: Maryland
city: Farmington Hills
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Cancer & Haematology Centre
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Mid North Coast Cancer Institute
state: New South Wales
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute
state: New South Wales
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Healthcare
state: Western Australia
city: Bruxelles - Brussel
country: Belgium
facility: Hôpital Erasme/Erasmus Ziekenhuis
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liege
country: Belgium
facility: CHU de Liège
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - UHN
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Besancon
country: France
facility: Hopital Jean Minjoz
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Lille Cedex
country: France
facility: Centre Oscar Lambret - Lille
city: Lyon Cedex
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: C.H.U. Timone
city: Nantes
country: France
facility: Centre René Gauducheau
city: Nice Cedex 2
country: France
facility: Centre Antoine Lacassagne
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: POITIERS cedex
country: France
facility: Hôpital de la Milétrie
city: Rennes Cedex
country: France
facility: Hôpital Pontchaillou
city: Rennes Cedex
country: France
facility: Centre Eugène Marquis - Rennes Cedex
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Bologna
country: Italy
facility: A.O.U. di Bologna Policlinico S.Orsola Malpighi
state: Emilia-Romagna
city: Modena
country: Italy
facility: A.O.U. di Modena - Policlinico
state: Emilia-Romagna
city: Milano
country: Italy
facility: Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Verona
country: Italy
facility: A.O.U.I. Verona
state: Veneto
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quirón de Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón | Oncología
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal | Oncología
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
state: Graubünden
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona
state: Ticino
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leicestershire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: North Ireland
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust (Surrey)
state: Surrey
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital (London)
city: Manchester
country: United Kingdom
facility: Christie Hospital
Study officials:
References: