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

• ClinicalTrials.gov Identifier: NCT02576548
• Recruitment Status: Completed
• First Posted: October 15, 2015
• Last Update Posted: June 18, 2019
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Tracking Information

• First Submitted Date: September 28, 2015
• First Posted Date: October 15, 2015
• Last Update Posted Date: June 18, 2019
• Actual Study Start Date: September 23, 2015
• Actual Primary Completion Date: May 23, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2015)

Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs). [ Time Frame: From Time of informed consent through 90 days after last dose of MEDI4276 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1/2 Study of MEDI4276 in Adults Subjects With Select HER2-expressing Advanced Solid Tumors.
• Official Title: 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
• Brief Summary: This research study is designed to evaluate an experimental drug, MEDI4276, in treating breast and stomach (gastric) cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HER2 Expressing Breast or Gastric/Stomach Cancers

Intervention

Biological: MEDI4276

MEDI4276 is an investigational product

Study Arms

• Experimental: MEDI4276 0.05 mg/kg
  Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.1 mg/kg
  Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.2 mg/kg
  Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.3 mg/kg
  Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.4 mg/kg
  Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.5 mg/kg
  Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.6 mg/kg
  Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.75 mg/kg
  Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276
• Experimental: MEDI4276 0.9 mg/kg
  Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.
  Intervention: Biological: MEDI4276

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2018): 47
• Original Estimated Enrollment (submitted: October 12, 2015): 120
• Actual Study Completion Date: May 23, 2018
• Actual Primary Completion Date: May 23, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02576548
• Other Study ID Numbers: D5760C00001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: MedImmune LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: MedImmune LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MedImmune LLC; Sponsor GmbH

• PRS Account: MedImmune LLC
• Verification Date: June 2019