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

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

Official Title
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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

Conditions
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HER2 Expressing Breast or Gastric/Stomach Cancers

Intervention / Treatment
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* Biological: MEDI4276


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer or gastric cancer refractory to standard therapy. 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. For subjects with gastric cancer: Prior treatment with a trastuzumab containing chemotherapy regimen is required. HER2 Positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue. At least one lesion measurable by RECIST Version 1.1. Exclusion Criteria: Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276. History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin >350 mg/m². Epirubicin >530 mg/m². Mitoxantrone >90 mg/m² and idarubicin > 70 mg/m². 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |