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

MedImmune

Status and phase: Completed; Phase 1

Conditions: HER2 Expressing Breast or Gastric/Stomach Cancers

Treatments: Biological: MEDI4276

Study type: Interventional

Funder types: Industry

Identifiers

NCT02576548

D5760C00001

Details and patient eligibility

About

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

Enrollment: 47 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 9 patient groups

MEDI4276 0.05 mg/kg

Experimental group

Description:

Participants received IV dose of 0.05 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.1 mg/kg

Experimental group

Description:

Participants received IV dose of 0.1 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.2 mg/kg

Experimental group

Description:

Participants received IV dose of 0.2 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.3 mg/kg

Experimental group

Description:

Participants received IV dose of 0.3 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.4 mg/kg

Experimental group

Description:

Participants received IV dose of 0.4 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.5 mg/kg

Experimental group

Description:

Participants received IV dose of 0.5 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.6 mg/kg

Experimental group

Description:

Participants received IV dose of 0.6 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.75 mg/kg

Experimental group

Description:

Participants received IV dose of 0.75 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276

MEDI4276 0.9 mg/kg

Experimental group

Description:

Participants received IV dose of 0.9 mg/kg MEDI4276 every three weeks (Q3W) for 2 years.

Treatment:

Biological: MEDI4276