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

NCT02699515 | Completed Phase 1 Results DMC

• 1 other identifier: 200647-0008
• Study Type: interventional
• Target: 114
• Locations: 3 countries
• Sites: 18

Brief Summary

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

Conditions

Solid Tumors

Keywords

MSB0011359C

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicity (DLT)

  A DLT was 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

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: 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 or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

  First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years

• Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: 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 or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

  First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years

Secondary Outcomes (12)

• Dose-Escalation Phase: Maximum Serum Concentration (Cmax) of M7824

  Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43

• Dose-Escalation Phase: Terminal Half Life (t1/2) of M7824

  Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43

• Dose-Escalation Phase: Area Under the Serum Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of M7824

  Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43

• Dose-Escalation Phase: Area Under The Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M7824

  Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43

• Dose-Escalation Phase: Number of Participants With Positive Serum Titers of Anti-Drug Antibodies of M7824

  Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years

Study Arms (1)

MSB0011359C (M7824)

EXPERIMENTAL

Drug: MSB0011359C

Interventions

MSB0011359C DRUG

Subjects with metastatic or locally advanced solid tumors received 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.

Also known as: M7824

MSB0011359C (M7824)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent and had signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
• Eligible male and female participants 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 had 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (18)

NHO Kyushu Cancer Center

Fukuoka, Japan

Location

National Cancer Center East, Department of Experimental Therapeutics

Kashiwa, Japan

Location

National Cancer Center East, Department of hepatobiliary and pancreatic oncology

Kashiwa, Japan

Location

Saitama Cancer Center

Kitaadachi-gun, Japan

Location

NHO Shikoku Cancer Center

Matsuyama, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

Kinki University Hospital

Sayama, Japan

Location

National Cancer Center, Department of Experimental Therapeutics

Tokyo, Japan

Location

National Cancer Center, Department of hepatobiliary and pancreatic oncology

Tokyo, Japan

Location

Kanagawa Cancer Center, Department of Gastroenterology

Yokohama, Japan

Location

Kanagawa Cancer Center, Department of Gastrointestinal Surgery

Yokohama, Japan

Location

Asan Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

Mackay Memorial Hospital

Taipei, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital; Linkou

Taoyuan District, Taiwan

Location

Related Publications (4)

• 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 TGFbeta and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia. Target Oncol. 2021 Jul;16(4):447-459. doi: 10.1007/s11523-021-00810-9. Epub 2021 Apr 11.

  PMID: 33840050 RESULT

• 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-beta and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1):e000564. doi: 10.1136/jitc-2020-000564.

  PMID: 32461347 RESULT

• Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.

  PMID: 36066618 DERIVED

• Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.

  PMID: 31278692 DERIVED

Related Links

• INTR@PID Clinical Trial Program
• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

Limitations and Caveats

Data collection and analysis of Pharmacokinetics of Cmin was omitted and not conducted due to business reason.

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: March 4, 2016
• Study Start: March 11, 2016
• Primary Completion: February 21, 2022
• Study Completion: February 21, 2022
• Last Updated: November 18, 2024
• Results First Posted: November 18, 2024

Record last verified: 2024-09

Locations

KR (3); JP (11); TW (4)