Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

MSB0010718C in Solid Tumors

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
EMD Serono Identifier:
First received: January 14, 2013
Last updated: February 11, 2015
Last verified: February 2015

This is a Phase 1, open-label, dose-escalation trial of MSB0010718C [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment has been closed for the following cohorts: non-small cell lung cancer (NSCLC), metastatic breast cancer (MBC), and metastatic colorectal cancer (mCRC).

Condition Intervention Phase
Solid Tumors
Drug: MSB0010718C
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0010718C in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

Resource links provided by NLM:

Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Dose Limiting Toxicity [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 [ Time Frame: Screening up to 10 weeks after last treatment ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters: AUC (0-t), AUC (0-infinity), λz, Cmax, Tmax, T(1/2) of MSB0010718C [ Time Frame: Every 6-week up to Week 25 ] [ Designated as safety issue: No ]
  • Immune-related Best Overall Response (irBOR) and Best Overall Response (BOR) according to modified Immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) , respectively [ Time Frame: Time from inclusion in the trial until the date of first documented progression or discontinuation from the study due to any cause, up to 1 year after last treatment ] [ Designated as safety issue: No ]
  • Immune-related Progression-Free Survival (irPFS) time and Progression-Free Survival (PFS) Time according to modified irRC and RECIST version 1.1 , respectively [ Time Frame: Time from inclusion in the trial until first observation of progressive disease or death when death occurs within 12 weeks of the last tumor assessment or first administration of trial treatment (whichever is later) up to 1 year after last treatment ] [ Designated as safety issue: No ]
  • Overall Survival Time [ Time Frame: Time from randomization to death anticipated up to 2 years after last treatment ] [ Designated as safety issue: No ]
  • Pharmacodynamic profile of MSB0010718C to include serum levels of cytokines [ Time Frame: Up to Week 25 ] [ Designated as safety issue: No ]
  • Number of subjects with anti-MSB0010718C antibodies [ Time Frame: Every 6-week up to Week 25 ] [ Designated as safety issue: No ]
  • Level of PD-L1 tumor expression [ Time Frame: Every 6-week up to Week 25 ] [ Designated as safety issue: No ]
  • Unconfirmed response according to RECIST 1.1 [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
  • Duration of response according to modified irRC and RECIST 1.1 [ Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 825
Study Start Date: January 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSB0010718C Drug: MSB0010718C
MSB0010718C (anti PD-L1) will be administered in study location using a protocol-defined dose escalation scheme until confirmed progression, unacceptable toxicity, or if any criterion for withdrawal from the trial or investigational medicinal product occurs. After determination of the dose and regimen for Expansion Phase, MSB0010718C will be administered to subjects divided into 3 primary cohorts of non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction (GEJ) cancer and metastatic breast cancer (MBC); and 7 secondary cohorts of colorectal cancer (CRC), castrate-resistant prostate cancer (CRPC), melanoma, ovarian cancer, adrenocortical carcinoma (ACC), mesothelioma, and urothelial carcinoma.
Other Name: anti PD-L1


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria for dose escalation and expansion phase:

  • Signed written informed consent
  • Male or female subjects aged greater than or equal to 18 years
  • Subjects must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
  • Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Effective contraception for both male and female subjects if the risk of conception exists
  • Other protocol defined inclusion criteria could apply

Inclusion Criteria for expansion phase:

  • Subjects must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
  • NSCLC: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Subjects should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA
  • Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Subjects should have received no more than 1 line of treatment for metastatic disease. Subjects should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 [HER2] positive). Subjects who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, subjects with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
  • MBC: Subjects must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Subjects must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Subjects must have received a taxane and an anthracycline, unless contra-indicated
  • Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, and urothelial carcinoma as defined in the protocol
  • Other protocol defined inclusion criteria for expansion phase could apply

Exclusion Criteria for dose escalation and expansion phase:

  • Concurrent treatment with a non-permitted drug
  • Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
  • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of MSB0010718C.
  • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
  • Rapidly progressive disease (for example, tumor lysis syndrome)
  • Active or history of central nervous system metastases
  • Receipt of any organ transplantation including allogeneic stem-cell transplantation
  • Significant acute or chronic infections as defined in the protocol
  • Active or history of any autoimmune disease (except for subjects with vitiligo) or immunodeficiencies
  • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
  • Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
  • Pregnancy or lactation period
  • Known alcohol or drug abuse
  • Clinically significant (that is, active) cardiovascular disease
  • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Legal incapacity or limited legal capacity
  • Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine
  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 identifier: NCT01772004

United States, Massachusetts
For Recruiting Locations in the United States, please Contact U.S. Medical Information
Rockland, Massachusetts, United States
Please contact the Merck KGaA Communication Center
Leuven, Belgium
Czech Republic
Please contact the Merck KGaA Communication Center
Praha, Czech Republic
Please contact the Merck KGaA Communication Center
Paris, France
Please contact the Merck KGaA Communication Center
Berlin, Germany
Please contact the Merck KGaA Communication Center
Budapest, Hungary
Korea, Republic of
Please contact the Merck KGaA Communication Center
Seoul, Korea, Republic of
Please contact the Merck KGaA Communication Center
Warszawa, Poland
Please contact the Merck KGaA Communication Center
Taipei, Taiwan
United Kingdom
Please contact the Merck KGaA Communication Center
London, United Kingdom
Sponsors and Collaborators
EMD Serono
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: EMD Serono Identifier: NCT01772004     History of Changes
Other Study ID Numbers: EMR 100070-001, 2013-002834-19
Study First Received: January 14, 2013
Last Updated: February 11, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Ministry of Health, Social and Family Affairs
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Korea: Ministry of Food and Drug Safety
Taiwan : Food and Drug Administration

Keywords provided by EMD Serono:
Solid Tumors
Phase 1
anti PD-L1
Non-small cell lung cancer (NSCLC)
Metastatic breast cancer (MBC)
Gastric and gastroesophageal junction (GEJ) cancer
Ovarian cancer
Colorectal cancer (CRC)
Castrate-resistant prostate cancer (CRPC)
Melanoma processed this record on February 27, 2015