First-in-Human Study of MS201408-0005A as Single Agent and in Combinations

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 1

Conditions: Metastatic or Locally Advanced Unresectable Solid Tumors

Treatments: Drug: M4112

Study type: Interventional

Funder types: Industry

Identifiers

NCT03306420

MS201408-0005

Details and patient eligibility

About

This is a Phase I, open-label study to determine the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD), and preliminary antitumor activity of MS201408-0005A as single agent (Part IA only) and in combination with MS201408-0005C or MS201408-0005B (Part IB, Part IC).

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects with histologically or cytologically proven advanced or metastatic solid malignancies for whom no effective standard therapy exists or has failed or subjects who are intolerant to established therapy known to provide clinical benefit for their condition (dose escalation cohorts; Part I).
• An eastern cooperative oncology group performance status (ECOG PS) of 0 to 1 at screening and adequate hematological, renal and hepatic function as defined by protocol specified criteria.
• Other protocol defined inclusion criteria could apply.

Exclusion criteria

• Intolerance to immune checkpoint inhibitor therapy as defined by the occurrence of an adverse drug reaction requiring drug discontinuation (dose escalation cohorts), concurrent anticancer treatment or immunosuppressive agents.
• Prior organ transplantation including allogeneic stem cell transplantation, brain metastases (except those meeting certain protocol specified criteria which are acceptable), significant acute or chronic infections, a history of cardiovascular/cerebrovascular disease.
• Current significant cardiac conduction abnormalities and hypokalemia as specified in the protocol.
• Warfarin or other Vitamin K antagonists treatment, strong inhibitors or inducers of cytochrome P450 (CYP)3A4, and drugs with a narrow therapeutic index, which are predominantly metabolized by CYP3A4 and drugs known to have a high risk to prolong QTc as per label.
• Pregnancy or lactation.
• Severe hypersensitivity reactions to monoclonal antibodies, known hypersensitivity to the investigational medicinal products or to one or more of the excipients, autoimmune diseases (inflammatory bowel diseases, interstitial lung disease, or pulmonary fibrosis), and live vaccines within 28 days prior to study entry.
• Pneumonitis and history of pneumonitis.
• Other protocol defined exclusion criteria could apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

15 participants in 5 patient groups

Part IA Dose Escalation: M4112 100 mg

Experimental group

Description:

Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Treatment:

Drug: M4112

Part IA Dose Escalation: M4112 200 mg

Experimental group

Description:

Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Treatment:

Drug: M4112

Part IA Dose Escalation: M4112 400 mg

Experimental group

Description:

Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Treatment:

Drug: M4112

Part IA Dose Escalation: M4112 600 mg

Experimental group

Description:

Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Treatment:

Drug: M4112

Part IA Dose Escalation: M4112 800 mg

Experimental group

Description:

Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Treatment:

Drug: M4112