A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors. (MEDI4276)

A Phase 1/2 Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogencity, and Antitumor Activity of MEDI4276 in Subjects With Select HER2-expressing Advanced Solid Tumors

This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.

Study Overview

• Status: Completed
• Conditions: HER2 Expressing Breast or Gastric/Stomach Cancers
• Intervention / Treatment: Biological: MEDI4276

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Research Site
  • Florida
    • Sarasota, Florida, United States, 34232
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.

2. Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy.

   1. For subjects with breast cancer:

      • Prior treatment with trastuzumab, pertuzumab, and T-DM1, either alone or in combination, is required.
      • Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor-positive or receptor-negative are eligible.
      • Prior hormone therapy is allowed, but last dose must be at least 14 days prior to first dose of MEDI4276.

   2. For subjects with gastric cancer:

      • Prior treatment with a trastuzumab containing chemotherapy regimen is required.
3. HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
4. At least one lesion measurable by RECIST Version 1.1.

Exclusion Criteria:

1. Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.

2. History of exposure to the following cumulative doses of anthracyclines:

   1. Doxorubicin or liposomal doxorubicin >350 mg/m².
   2. Epirubicin >530 mg/m².
   3. Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m².
   4. If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 350 mg/m² of doxorubicin.
3. Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery or other therapy to control symptoms from brain metastases within 2 months prior to first dose of MEDI4276.

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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI4276 0.05 mg/kg; Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.1 mg/kg; Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.2 mg/kg; Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.3 mg/kg; Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.4 mg/kg; Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.5 mg/kg; Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.6 mg/kg; Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.75 mg/kg; Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product
Experimental: MEDI4276 0.9 mg/kg; Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.	Biological: MEDI4276; MEDI4276 is an investigational product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs).	The maximum tolerated dose/maximum administered dose will be determined by the number of participants experiencing DLTs. The safety profile will be assessed through number of participants experiencing AEs, SAEs, abnormal laboratory parameters, vital signs and electrocardiogram (ECG) results.	From Time of informed consent through 90 days after last dose of MEDI4276

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR	Time from Informed Consent up to 3 years
Peak Plasma Concentration (Cmax)	The immunogenicity of MEDI4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)	From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product
Progression-free survival (PFS)	Progression-free survival will be measured from the start of treatment with MEDI4276 until the first documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.	Estimated to be from time of informed consent up to 3 years
Overall survival (OS)	Overall survival will be determined as the time from the start of treatment with MEDI4276 until death due to any cause.	Estimated to be from time of informed consent up to 3 years
Area under the plasma concentration versus time curve (AUC)	The immunogencity of MEDI 4276 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).	From first dose of MEDI4276 through to 30 days after the last dose of investigational product

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

General Publications

• Faria M, Peay M, Lam B, Ma E, Yuan M, Waldron M, Mylott WR Jr, Liang M, Rosenbaum AI. Multiplex LC-MS/MS Assays for Clinical Bioanalysis of MEDI4276, an Antibody-Drug Conjugate of Tubulysin Analogue Attached via Cleavable Linker to a Biparatopic Humanized Antibody against HER-2. Antibodies (Basel). 2019 Jan 11;8(1):11. doi: 10.3390/antib8010011.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2015
• Primary Completion (Actual): May 23, 2018
• Study Completion (Actual): May 23, 2018

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: October 12, 2015
• First Posted (Estimate): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: June 14, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: D5760C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No