M8891 First in Human in Solid Tumors

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 1

Conditions: Metastatic Renal Cell Carcinoma; Advanced Solid Tumors

Treatments: Drug: Part 1: M8891

Study type: Interventional

Funder types: Industry

Identifiers

NCT03138538

MS100015_0019

Details and patient eligibility

About

The purpose of this study was to determine the maximum tolerated dose (MTD), safety, tolerability, Pharmacokinetic (PK), pharmacodynamic and clinical activity of M8891 as single agent in participants with advanced solid tumors in Part 1.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must be refractory to or intolerant of existing cancer therapy(ies) known to provide clinical benefit.
• Histologically confirmed advanced solid tumors with no clear curative treatment options available after at least 1 prior systemic anticancer therapy.
• Tumor accessible for biopsies and agreement to conduct pre-dose and post-dose fresh tumor biopsies.
• Male or female subjects at least 18 years of age
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening
• Histologic or cytologic evidence/proven of metastatic renal cell carcinoma (mRCC) with clear cell component
• Part 2A: Participants should have progressed to 1 or more previous lines of systemic anticancer therapy, excluding treatment with cabozantinib
• Part 2B: Participants should have progressed to 1 or 2 previous lines of systemic anticancer therapy, excluding treatment with cabozantinib. Participants should have failed to only 1 previous TKI for metastatic disease. Adjuvant therapy with sunitinib will be considered as 1 line of therapy for metastatic disease in the case that disease progression occurs during or within 3 months of the completion of the treatment.
• Other protocol defined inclusion criteria could apply

Exclusion criteria

• ECOG PS >= 2
• Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years of study start.
• Severe bone marrow, renal or liver impairment.
• Tumor in contact with, invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions
• Uncontrolled hypertension defined as sustained Blood Pressure (BP) > 150 millimeters of mercury (mm Hg) systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
• Participant is pregnant or breastfeeding
• Part 2A and 2B: Previous use of cabozantinib or a MetAP2 inhibitor, tumor in contact with invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions
• Other protocol defined exclusion criteria could apply

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 6 patient groups

M8891 7 mg

Experimental group

Description:

Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891

M8891 12 mg

Experimental group

Description:

Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891

M8891 20 mg

Experimental group

Description:

Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891

M8891 35 mg

Experimental group

Description:

Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891

M8891 60 mg

Experimental group

Description:

Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891

M8891 80 mg

Experimental group

Description:

Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Treatment:

Drug: Part 1: M8891