First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies

Summary

This is a Phase 1, first-in-human, open-label, non-randomized, dose escalation, trial to explore the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity signals of MSC2363318A.

Conditions

• Solid Tumor

Interventions

DRUG

MSC2363318A

Part 1: MSC2363318A will be administered orally once daily for repeated 21-day cycles until intolerable toxicity or disease progression. Additional dose escalations will continue until Maximum Tolerated Dose (MTD) is reached, the food effect will be investigated in a separate group. Part 2 (Cohort 1): MSC2363318A will be administered orally once daily for repeated 21-day cycles until intolerable toxicity or disease progression in subjects with PAM pathway alterations. Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle).

DRUG

MSC2363318A plus Trastuzumab

Part 2 Cohort 2: MSC2363318A will be administered orally once daily for repeated 21-day cycles in combination with Trastuzumab. Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle). Trastuzumab is a recombinant IgGI kappa humanized monoclonal antibody administered weekly by intravenous infusion.

DRUG

MSC2363318A plus Tamoxifen

Part 2 Cohort 3: MSC2363318A will be administered orally once daily for repeated 21-day cycles in combination with Tamoxifen. Dose reductions or treatment interruptions will be made at the discretion of the Investigator. If treatment interruption is required due to an acute or less severe but intolerable MSC2363318A-related event, at least a 1-week break is recommended. If, at retreatment, the dose reduction is not required, then the "continuous daily dosing regimen" may be replaced with an "intermittent dose regimen" of 2 weeks on, 1 week off (i.e. daily dosing from Day 1 to Day 15 followed by no dosing on Day 16 to Day 21 of the cycle). Tamoxifen is a nonsteroidal antiestrogen administered daily by oral administration.

Sponsors & Collaborators

• EMD Serono

  lead INDUSTRY

Principal Investigators

• Medical Responsible · EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-12-13

Primary Completion

2018-08-09

Completion

2018-08-09

FDA Drug

Yes

Countries

• United States

Study Locations