Study of Samalizumab in Patients With Advanced Cancer

A Multicenter, Dose-Escalation, Phase 1 Study of Samalizumab (ALXN6000) to Evaluate the Pharmacokinetics, Safety, and Tolerability in Patients With Advanced Cancer

This is a multicenter, open-label, dose-escalation, Phase 1 study of intravenous (IV) samalizumab to determine its maximum tolerated dose (MTD), overall safety/tolerability, pharmacokinetic and pharmacodynamic parameters, and efficacy in participants with advanced cancer. The study was terminated for administrative reasons and not due to any safety concerns.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Samalizumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female participant was ≥ 18 years of age at Screening.
2. Eastern Cooperative Oncology Group performance status of 0 to 2.
3. Participant had advanced/metastatic cancer with disease progression after treatment with all available therapies known to confer clinical benefit.
4. Participant had a life expectancy of greater than 12 weeks.

Exclusion Criteria:

1. Participant had a symptomatic brain metastasis.
2. Participant had active gastrointestinal bleeding as evidenced by either hematemesis or melena.
3. Participant had acute gastrointestinal ulcers.
4. Participant had a history of any cancer other than the present condition (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 3 years.
5. Participant with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
6. Participant had an active infection requiring therapy.
7. Participant's serum was positive for the presence of hepatitis B surface antigen, antibodies to hepatitis C virus, or antibodies to human immunodeficiency virus 1/2.
8. Participant had significant cardiovascular impairment (history of New York Heart Association Functional Classification system Class III or IV) or a history of myocardial infarction or unstable angina within the past 6 months prior to study drug treatment.

9. The participant's most recent test values within 14 days before the date of entry met the following standards:

   • Bone marrow function: neutrophil count ≤1500/millimeter (mm)^3, hemoglobin ≤9.0 grams/deciliter, platelet count ≤100,000/mm^3.
   • Liver function: total bilirubin ≥1.5 x the upper limit of normal (ULN) based on the standard value of each institution, aspartate aminotransferase and alanine aminotransferase ≥2.5 x ULN based on the reference laboratory.
   • Renal function: serum creatinine ≥1.5 x ULN based on the reference laboratory.
10. Participant had ongoing immune-stimulated adverse events from other immunotherapies (for example, pneumonitis, thyroiditis, or hepatitis) or a history of pneumonitis.
11. Participant had received chemotherapy, targeted therapy, and/or immunotherapy within the 28 days prior to first dose of study drug, or within a Washout Period for the chemotherapy, targeted therapy, and/or immunotherapy of 5 half-lives, whichever occurred first.
12. Participant had toxicities from previous immunotherapy that had not resolved to Grade 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Samalizumab 10, 15, 20 milligrams (mg)/kilogram (kg) Dose; Participants received escalating doses of 10, 15, and 20 mg/kg of samalizumab IV every 21 days. Enrollment at each dose level and safety assessments were completed prior to enrolling at the next dose level; intra-participant dose escalation was not allowed. 3 participants were enrolled into a dose cohort: If 0/3 participants developed dose limiting toxicities (DLT) within Cycle 1, enrollment began at the next higher dose to a maximum of 20 mg/kg. If 1/3 participants developed a DLT, the dose cohort was expanded to include 3 new participants. If 0/3 new participants developed a DLT within Cycle 1, enrolment began at the next higher dose level. If ≥1 of 3 new participants developed a DLT within Cycle 1, dose-escalation was terminated, and the dose level 5 mg/kg below the current dose was considered the MTD. If ≥2 of 3 participants developed DLTs within Cycle 1, dose-escalation was terminated, and the dose level 5 mg/kg below the current dose was considered the MTD.

Drug: Samalizumab; Samalizumab is a humanized, anti CD200 monoclonal antibody provided as a sterile 5 mg/milliliters (mL) solution for IV administration.; Other Names: ALXN6000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Of Participants Experiencing DLT Graded According To CTCAE Version 4.03, Observed In The Cycle 1 In Order To Meet The Objective Of Assessment Of The MTD	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety monitoring began at the informed consent obtained and continued up to 28 days after the last dose of samalizumab or until new anti-tumor therapy, whichever was earlier.
Maximum Plasma Concentration After Administration Of Samalizumab		21 days in Cycle 1
Area Under The Plasma Drug Concentration-time Curve After Administration Of Samalizumab		21 days in Cycle 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate Using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	Up to 2 Years
Disease Control Rate Using RECIST 1.1	Up to 2 Years
Duration Of Response	Up to 2 Years
Progression Free Survival	Up to 2 Years
Overall Survival	Up to last participant completing at least 6 months

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals
• Collaborators: Quintiles, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2016
• Primary Completion (Actual): September 12, 2017
• Study Completion (Actual): September 27, 2017

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 8, 2016
• First Posted (Estimate): December 9, 2016

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Phase 1; Solid tumor
• Other Study ID Numbers: ALXN6000-ONC-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No