Clinical trial NCT02576548: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HER2 Expressing Breast or Gastric/Stomach Cancers
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-10-15
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs) and dose-limiting (DLTs).
timeFrame: From Time of informed consent through 90 days after last dose of MEDI4276
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Time from Informed Consent up to 3 years
measure: Peak Plasma Concentration (Cmax)
timeFrame: From first dose of MEDI4276 thorugh to 30 days after last dose of investigational product
measure: Progression-free survival (PFS)
timeFrame: Estimated to be from time of informed consent up to 3 years
measure: Overall survival (OS)
timeFrame: Estimated to be from time of informed consent up to 3 years
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From first dose of MEDI4276 through to 30 days after the last dose of investigational product
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Research Site
state: California
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
Study officials:
affiliation: Sponsor GmbH
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: 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.