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Brief Title: Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer

A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination With Pembrolizumab and in Combination With MGA012 in Patients With Melanoma, Squamous Cell Cancer of the Head and Neck, Non-Small Cell Lung Cancer, Urothelial Cancer, and Other Cancers

INTRODUCTION

  • Org Study ID: CP-MGA271-03
  • Secondary ID: N/A
  • NCT ID: NCT02475213
  • Sponsor: MacroGenics

BRIEF SUMMARY


The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination
with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous
cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), Urothelial
Cancer and other B7-H3 expressing cancers. The study will also evaluate what is the highest
dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments
will also be done to see how the drug acts in the body (pharmacokinetics (PK),
pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with
pembrolizumab. Safety and efficacy of enoblituzumab in combination with MGA012 (anti-PD-1
monoclonal antibody; also known as INCMGA00012) will also be evaluated.

DETAILED DESCRIPTION


This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up
study of enoblituzumab administered intravenously (IV) on a weekly schedule for up to 51
doses in combination with IV pembrolizumab administered on an every-3-week schedule for up to
17 doses.

The dose escalation phase is designed to characterize the safety and tolerability of the
combination of enoblituzumab and pembrolizumab and to define the maximum tolerated or maximum
administered dose (MTD/MAD). Patients with methothelioma, urethelial cancer, NSCLC, SCCHN,
clear cell renal cell carcinoma (ccRCC), ovarian cancer, melanoma, thyroid cancer, triple
negative breast cancer (TBNC), pancreatic cancer, colon cancer, soft tissue sarcoma, or
prostate cancer will be enrolled in this study phase. An additional dose escalation cohort of
up to 15 patients is designed to characterize the safety and tolerability of the combination
of enoblituzumab and MGA012 in patients with melanoma, SCCHN, NSCLC, urothelial cancer, and
other cancers, and any dose level not exceeding the MTD may be expanded to further evaluate
safety and efficacy of this combination.

During the Cohort Expansion Phase, additional cohorts of patients with B7-H3 expressing
unresectable, locally-advanced or metastatic melanoma (up to n=16), 2 cohorts of NSCLC (n= up
to 20 in each cohort), 2 cohorts of SCCHN (up to n=20 in each cohort) or urothelial cancer
(up to n=16) will be enrolled to receive MGA271 in combination with pembrolizumab at the MTD
(or MAD) established from the Dose Escalation Phase of the study.

The efficacy follow-up period consists of the 2-year period after the final dose of study
drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid
Tumors (RECIST) and immune-related response criteria (irRC).


  • Overall Status
    Recruiting
  • Start Date
    July 2015
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with adverse events

Primary Outcome 1 - Timeframe: one year

CONDITION

  • Melanoma
  • Head and Neck Cancer
  • Non Small Cell Lung Cancer
  • Urethelial Carcinoma

ELIGIBILITY


Inclusion Criteria:

- Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN,
NSCLC, and other cancers that express B7-H3.

- Melanoma that has progressed during or following at least 1 and up to 5 prior systemic
treatments for unresectable locally advanced or metastatic disease, or melanoma
patients who are intolerable of or have refused standard cancer therapy. Pre- and
on-study biopsy required.

- SCCHN that has progressed during or following at least 1 and up to 5 prior systemic
treatments for metastatic or recurrent disease deemed to be incurable. Patient who
refuse radical resection for recurrent disease or are intolerant of or refused
standard first line therapy are eligible to enroll

- NSCLC that has progressed during or following 1 - 5 prior systemic therapies for
unresectable locally advanced or metastatic disease (at least one docetaxel,
gemcitabine, or platinum analogue based therapy), or are intolerant of or refused
standard cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known
activating mutation: the prior systemic therapy is at least one platinum analogue. For
adenocarcinoma with known activating driver mutation: the prior systemic therapy is at
least TKI directed

- Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has
progressed during or following at least 1 and up to 5 prior systemic treatments for
unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1,
but excludes other experimental therapies). Patients must have received at least one
platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense
methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or
carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.

- Measurable disease per RECIST 1.1 criteria

- Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

- Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

- Patients with a history of symptomatic central nervous system metastases, unless
treated and asymptomatic

- Patients with history of autoimmune disease with certain exceptions such as vitiligo,
resolved chilhood atopic dermatitis, psoriasis not requiring systemic therapy within
the past 2 years, patients with history of Grave's disease that are now euthyroid
clinically and by lab testing

- History of allogeneic bone marrow, stem cell, or solid organ transplant

- Treatment with systemic cancer therapy or investigational therapy within 4 weeks of
first study drug administration; radiation within 2 weeks; corticosteroids (greater
than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive
drugs within 2 weeks of first study drug administration

- Trauma or major surgery within 4 weeks of first study drug administration

- History of clinically-significant cardiovascular disease; gastrointestinal
perforation; gastrointestinal bleeding, acute pancreatitis or diverticulitis within 4
weeks of first study drug administration

- Active viral, bacterial, or systemic fungal infection requiring parenteral treatment
within 7 days of first study drug administration

- Known history of hepatitis B or C infection or known positive test for hepatitis B
surface antigen or core antigen, or hepatitis C polymerase chain reaction (PCR)

- Known positive testing for human immunodeficiency virus or history of acquired immune
deficiency syndrome

- Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient
contained in the drug or vehicle formulation for MGA271 or pembrolizumab.

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Stacie Goldberg, M.D.

Role: Study Director

Affiliation: MacroGenics

Overall Contact

Name: Stacie Goldberg, M.D.

Phone: 240-552-8104

Email: cavallor@Macrogenics.com

LOCATION

Facility Status Contact
Facility: Moffitt Cancer Center
Tampa, Florida 33612
United States 		Status: Recruiting Contact: Kristina Trajic
813-745-4673
Kristina.trajic@moffitt.org
Facility: South Texas Accelerated Research Therapeutics, LLC - Midwest
Grand Rapids, Michigan 49503
United States 		Status: Recruiting Contact: Kathy Estkowski
616-954-5551
kathy.estkowski@startmidwest.com
Facility: Nebraska Cancer Specialists
Omaha, Nebraska 68130
United States 		Status: Recruiting Contact: Gladys Pierce
402-690-6972
gpierce@nebraskacancer.com
Facility: Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89169
United States 		Status: Recruiting Contact: AnaArlene Ramirez, RN
702-952-3406
anaarlene.ramirez@usoncology.com
Facility: Hospital of the University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania 19104
United States 		Status: Recruiting Contact: Maryann Redlinger, RN
215-662-7452
maryann.redlinger@uphs.upenn.edu
Facility: University of Pittsburg
Pittsburgh, Pennsylvania 15232
United States 		Status: Recruiting Contact: Sara Forder, BSN, RN
412-623-8961
forderse@upmc.edu

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