MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

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

The main purpose of this Phase I study was to test MSB0011359C (M7824) at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Phase I means the study drug has not previously been given to humans or has only been given to a limited number of people, although it has been extensively studied in animals. Based on this information, it is hoped to find out which dose could be best for the treatment of patients. There are two parts of this research study: a dose-escalation part and an expansion part. Dose escalation means that the first people taking part in the study will receive low doses of the study drug, and as more people take part, the additional participants will receive a higher dose. This is done to find the safest dose for the study drug. Expansion means that after the dose-escalation part of the study has looked at the safety and effectiveness of different doses, many more people will be invited to take part in the study and will receive the study drug at the safest dose. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

This is a Phase I, open-label, dose-escalation trial with consecutive parallel-group expansion in selected solid tumor indications. The current trial wascomposed of a standard dose escalation "3 + 3" cohort design, for which 3 to 6 subjects will be enrolled at each dose level depending on the occurrence of dose limiting toxicities (DLTs), followed by a consecutive parallel-group expansion in selected solid tumor in dications. Cohorts of 3 subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or standard therapy has failed, will receive MSB0011359C (M7824) at escalating dose levels. After determination of the Maximum tolerated dose (MTD), enrollment in several expansion cohorts will be opened to determine the safety, pharmacokinetic (PK) / Pharmacodynamic, and clinical activity of MSB0011359C (M7824). Subjects who have experienced a confirmed complete response (CR) should continue treatment through the end of 12 months, although additional treatment is possible. In the case of progressive disease (PD), subjects should continue treatment through their next tumor assessment. Additional indications will be planned based on emerging data in the field.

Inclusion Criteria:

• Ability to understand the purpose of the study, provide signed and dated informed consent, and able to comply with all procedures
• In Japan, if a subject is < 20 years, the written informed consent from his/her parent or guardian will be required in addition to the subject's written consent
• Male or female subjects aged greater than or equal to (>=) 18 years
• Life expectancy >= 12 weeks as judged by the Investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry
• Disease must be measurable with at least 1 uni dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• 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.

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 radiotherapy delivered in a normal organ-spearing technique), immune therapy, or cytokine therapy
• Major surgery within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted)
• 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) within the last 3 years. Subjects with history of cervical carcinoma in situ, superficial or non invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded. Subjects with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor.
• Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
• Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded
• 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)

Other protocol-defined exclusion criteria could apply