MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02699515
• Other study ID #: 200647-0008
• Status: Completed
• Phase: Phase 1
• Start date: March 11, 2016
• Est. completion date: February 21, 2022

Study information

• Verified date: March 2022
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is assess the safety and tolerability of MSB0011359C. Study consists of dose-escalation part and an expansion part in subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or a standard therapy has failed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: February 21, 2022
• Est. primary completion date: February 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Able and willing to give written informed consent and has signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
• Eligible male and female subjects aged greater than or equal to (>=)20 years
• Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no effective standard therapy exists or standard therapy has failed
• Eastern Cooperative Oncology Group performance status (ECOG) performance status of 0 to 1 at trial entry
• Life expectancy >=12 weeks as judged by the Investigator.
• Adequate hematological function defined by white blood cell (WBC) count >=3*10^9/Liter with absolute neutrophil count (ANC) >=1.5*10^9/Liter, lymphocyte count >=0.5* 10^9/Liter, platelet count >=75*10^9/Liter, and Hemoglobin (Hgb) >= 9 grams per deciliter (g/dL) (in absence of blood transfusion).
• Adequate hepatic function defined by a total bilirubin level <=1.5 × Upper limit of normal (ULN), an AST level <= 2.5 × ULN, and an ALT level <= 2.5 × ULN.
• Adequate renal function defined by an estimated creatinine clearance >50 milliliter per minute (mL/min) according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24 hour urine collection. Other protocol-defined exclusion criteria could apply.

Exclusion Criteria:

• Concurrent treatment with non-permitted drugs and other interventions
• Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy
• Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy)
• Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
• Previous malignant disease other than the target malignancy to be investigated in this trial with the exception of cervical carcinoma in situ and superficial or non invasive bladder cancer (treated with curative intent) within the last 5 years or basal cell or squamous cell carcinoma in situ within the last 3 years
• Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
• Active or history of central nervous system metastases, except as in the melanoma-specific Central nervous system (CNS) criteria listed above
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant)

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• MSB0011359C
Subjects with metastatic or locally advanced solid tumors will receive intravenous infusion of MSB0011359C over 1 hour once every two weeks for up to 12 months until confirmed progressive disease (PD), unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.

Locations

Country	Name	City	State
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center East, Department of Experimental Therapeutics	Kashiwa
Japan	National Cancer Center East, Department of hepatobiliary and pancreatic oncology	Kashiwa
Japan	Saitama Cancer Center	Kitaadachi-gun
Japan	NHO Shikoku Cancer Center	Matsuyama
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Kinki University Hospital	Osakasayama
Japan	National Cancer Center, Department of Experimental Therapeutics	Tokyo
Japan	National Cancer Center, Department of hepatobiliary and pancreatic oncology	Tokyo
Japan	Kanagawa Cancer Center, Department of Gastroenterology	Yokohama
Japan	Kanagawa Cancer Center, Department of Gastrointestinal Surgery	Yokohama
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital; Linkou	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

References & Publications (2)

Lin CC, Doi T, Muro K, Hou MM, Esaki T, Hara H, Chung HC, Helwig C, Dussault I, Osada M, Kondo S. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFß and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort i — View Citation

Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-ß and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Canc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with DLT (Dose limiting Toxicity): dose escalation part	A DLT is defined as any grade greater than or equal to (>=) 3 adverse event suspected to be related to investigational medicinal product (IMP) by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment.	Baseline up to Week 3
Primary	Number of Subjects with treatment-emergent adverse events (TEAEs)	An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. AEs (SAEs and non-SAEs) will be considered TEAEs when emerging on treatment period defined as the time from the first trial drug administration up to 30 days after the last drug administration date or the earliest date of subsequent anticancer drug therapy minus 1 day, whichever occurs first, unless otherwise stated.	First trial drug administration up to 30 days after the last drug administration assessed up to 2 years
Primary	Number of subjects with treatment-related Adverse Events (AE)	Treatment related AEs are any untoward medical occurrence in a subject who received study drug with causal relationship with the investigational product as assessed by the investigator.	First trial drug administration up to 30 days after the last drug administration assessed up to 2 years
Secondary	Maximum serum concentration (Cmax) of MSB0011359C		Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Secondary	Minimum serum concentration (Cmin) of MSB0011359C		Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Secondary	Area under the concentration time curve from zero to last sampling time (AUC0-t) of MSB0011359C		Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Secondary	Area under the concentration time curve from time zero to infinity (AUC0-inf) of MSB0011359C		Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Secondary	Terminal half life (t1/2) of MSB0011359C		Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43
Secondary	Serum titers of anti-MSB0011359C antibodies		Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years
Secondary	Best Overall Response (BOR) as assessed by investigator: Dose escalation part	BOR will be assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.	Date of randomization up to 2 years
Secondary	Best Overall Response (BOR) as assessed by investigator: Expansion part	BOR will be assessed by investigator according to RECIST Version 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD.	Date of randomization up to 2 years
Secondary	Best Overall Response (BOR) as assessed by Independent Endpoint Review Committee (IRC): Expansion part	The BOR per Independent Endpoint Review Committee (IRC) adjudication will be determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD.	Date of randomization up to 2 years
Secondary	Duration of response	Time from first assessment of CR to disease progression or death, for TLs, CR was defined as the disappearance of all TLs	Date of randomization up to 2 years
Secondary	Disease control rate	The disease control rate is defined as the percentage of subjects with BOR. The BOR per IRC adjudication will be determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD.	Date of randomization up to 2 years
Secondary	Progression Free survival (PFS) time	PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS will be assessed as RECIST v1.1 as adjudicated by IRC. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Date of randomization until death or progressive disease assessed up to 2 years
Secondary	Overall Survival (OS) time	OS is defined as the time from randomization to death due to any cause.	Date of randomization until death assessed up to 2 years

External Links

•   INTR@PID Clinical Trial Program
•   Trial Awareness and Transparency website