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

Neoplasms Clinical Trial

— ARCS-Multi  

Official title:

Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03102320
• Other study ID #: 15834
• Secondary ID: 2016-004002-33
• Status: Completed
• Phase: Phase 1
• Start date: May 26, 2017
• Est. completion date: July 26, 2021

Study information

• Verified date: June 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 173
• Est. completion date: July 26, 2021
• Est. primary completion date: September 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Cisplatin
Cisplatin 25 mg/m2 IV administered on day 1 and day 8 of 21 day cycle, for up to maximum 6 cycles
• Gemcitabine
Gemcitabine 1000 mg/m2 IV administered on days 1 and 8 of a 21-day cycle
• 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

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Blacktown Cancer & Haematology Centre	Blacktown	New South Wales
Australia	Mid North Coast Cancer Institute	Coffs Harbour	New South Wales
Australia	Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Epworth HealthCare	Richmond	Victoria
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	St John of God Healthcare	Subiaco	Western Australia
Belgium	Hôpital Erasme/Erasmus Ziekenhuis	Bruxelles - Brussel
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHU de Liège	Liege
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University Health Center	Montreal	Quebec
Canada	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre - UHN	Toronto	Ontario
France	Hopital Jean Minjoz	Besancon
France	Hôpital Henri Mondor	Creteil
France	Centre Oscar Lambret - Lille	Lille Cedex
France	Centre Léon Bérard	Lyon Cedex
France	C.H.U. Timone	Marseille
France	Centre René Gauducheau	Nantes
France	Centre Antoine Lacassagne	Nice Cedex 2
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Hôpital de la Milétrie	POITIERS cedex
France	Centre Eugène Marquis - Rennes Cedex	Rennes Cedex
France	Hôpital Pontchaillou	Rennes Cedex
France	Institut Gustave Roussy	Villejuif Cedex
Italy	A.O.U. di Bologna Policlinico S.Orsola Malpighi	Bologna	Emilia-Romagna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	A.O.U. di Modena - Policlinico	Modena	Emilia-Romagna
Italy	A.O.U.I. Verona	Verona	Veneto
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Nederlands Kanker Instituut	Amsterdam
Netherlands	Maastricht UMC	Maastricht
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Spain	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	Hospital General Universitario Gregorio Marañón | Oncología	Madrid
Spain	Hospital Ramón y Cajal | Oncología	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Universitario Quirón de Madrid	Pozuelo de Alarcón	Madrid
Switzerland	Ospedale Regionale Bellinzona	Bellinzona	Ticino
Switzerland	Kantonsspital Graubünden	Chur	Graubünden
United Kingdom	Belfast City Hospital	Belfast	North Ireland
United Kingdom	Leicester Royal Infirmary	Leicester	Leicestershire
United Kingdom	Guy's Hospital	London
United Kingdom	Royal Marsden Hospital (London)	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Royal Marsden NHS Trust (Surrey)	Sutton	Surrey
United States	National Cancer Institute - Maryland	Bethesda	Maryland
United States	Texas Oncology, PA	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Farmington Hills	Michigan
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Southern California	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Medical Center - New Orleans	New Orleans	Louisiana
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Stanford Health Care	Stanford	California
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Bayer	ImmunoGen, Inc., MorphoSys AG

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients in the safety lead-in (SLI) phase who completed Cycle 1 or had a DLT and were not replaced.	During SLI, patients with cholangiocarcinoma received anetumab ravtansine in combination with cisplatin and patients with pancreatic adenocarcinoma received anetumab ravtansine in combination with gemcitabine. The highest dose of anetumab ravtansine that can be given so that not more than 1 out of 6 patients experiences a dose-limiting toxicity (DLT) during the DLT evaluation period were declared as the MTD for anetumab ravtansine in combination with cisplatin or with gemcitabine.	At least 3 weeks after the last patient starts treatment
Primary	Objective response (qualitative improvement from baseline) of anetumab ravtansine for monotherapy and combination therapy in mesothelin expressing advanced solid tumors	A patient is a responder if the patient has a best response compared to baseline of complete response (CR) or partial response (PR) among all post-baseline tumor assessments, as determined per RECIST 1.1 criteria (ITMIG modified RECIST 1.1 criteria for thymic carcinoma)	Up to approximately 26 months after patient starts treatment
Primary	Durable disease control (lack of progression from baseline) of anetumab ravtansine in indications pancreatic and gastric cancer (co-primary endpoint)	A patient experiences durable disease control if the patient has a tumor response compared to baseline of CR, PR or stable disease (SD) among the post-baseline tumor assessments made at least 180 days from first treatment, without prior disease progression	Up to approximately 26 months after patient starts treatment
Secondary	Number of serious and non-serious adverse events (AEs)	Include treatment-emergent AEs, SAEs, treatment-related AEs, AEs of special interest, and deaths.	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)
Secondary	Disease control rate (DCR)	The DCR is defined as the number of patients with disease control divided by the number of treated patients.	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]
Secondary	Duration of response (DOR)	DOR is defined in responders as the time from documentation of tumor response (CR or PR) to earlier of disease progression or death	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]
Secondary	Durable response rate (DRR)	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.	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]
Secondary	Progression free survival (PFS)	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.	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]
Secondary	Durable disease control rate (DDCR) of anetumab ravtansine in indications other than pancreatic and gastric cancer	A patient experiences durable disease control if the patient has a tumor response of CR, PR or SD with CR, PR or SD assessed at least 180 days from first treatment, without prior progression.	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]

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