A Phase 1, First-in-Human, Open-Label, Dose Escalation and Cohort Expansion Study of MGD019, a Bispecific DART® Protein Binding PD-1 and CTLA-4 in Patients With Unresectable or Metastatic Neoplasms

Who is this study for? Adult patients with Solid Tumors
What treatments are being studied? MGD019 Bispecific DART Protein Binding PD-1 and CTLA-4
Status: Active_not_recruiting
Location: See all (39) locations...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of lorigerlimab. This Phase 1, open-label study will characterize safety, dose-limiting toxicities (DLTs), and maximum tolerated/administered dose (MTD/MAD) of MGD019. Dose escalation will occur in a 3+3+3 design in patients with advanced solid tumors of any histology. Once the MTD/MAD is determined, a Cohort Expansion Phase will be enrolled to further characterize safety and initial anti-tumor activity in patients with specific tumor types anticipated to be sensitive to dual checkpoint blockade.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Dose escalation: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or patients who are intolerant to standard therapy.

• Cohort Expansion Phase:

• Checkpoint inhibitor-naïve squamous cell NSCLC, including:

‣ Patients that have progressed during or following treatment with platinum-based chemotherapy for advanced disease. Patients harboring an activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement must have progressed following at least one available EGFR or ALK targeted therapy. ROS1 rearrangement or BRAF mutation must have progressed following at least 1 available EGFR (including osimertinib for EGFR T790M-mutated NSCLC), ALK, ROS1 or BRAF targeted therapy, respectively

⁃ Patients that have progressed during or following treatment with platinum-based chemotherapy for advanced disease and patients with previously untreated squamous cell NSCLC without activating mutations for whom checkpoint inhibitor therapy is not approved or available.

• Advanced non-microsatellite instability-high colorectal cancer (CRC) with recurrence, progression, or intolerance to standard therapy consisting of at least 2 prior standard regimens. CRC harboring an activating EGFR mutation must have progressed during or following at least one available EGFR targeted therapy. Patients who are inappropriate candidates for or have refused treatment with these regimens are also eligible. Patients should have received no more than 4 prior lines of systemic therapy.

• Checkpoint inhibitor-naïve mCRPC that has progressed during or following no more than 2 prior lines of an androgen receptor antagonist or androgen synthesis inhibitor (e.g., enzalutamide or abiraterone, respectively), if approved and available, with a PSA value of at least 2 ng/mL and meeting at least one of the following:

• Progression in measurable disease (RECIST v1.1).

• Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG-2).

• Rising PSA defined as at least two sequential rises in PSA.

• Eligible patients may have received prior chemotherapy (i.e. docetaxel), and patients with known homologous recombination (HRR) pathway gene alterations must have received the applicable approved therapy (e.g. olaparib).

• Cutaneous melanoma that has progressed during or following systemic treatment for unresectable, locally advanced, or metastatic disease. Patients will have received PD-(L)1 and/or CTLA-4 pathway inhibitors where available and indicated.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Life expectancy ≥ 12 weeks.

• Measurable disease as per RECIST 1.1 for the purpose of response assessment must either (a) not reside in a field that has been subjected to prior radiotherapy or (b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment.

• All patients must have an identified formalin-fixed, paraffin embedded (FFPE) tumor specimen (up to 20 slides or a block) for immunohistochemical evaluation of pharmacodynamic markers of interest. Patients may undergo a fresh tumor biopsy during the screening period if a tumor sample is not available. Patients in the mCRPC expansion cohort with bone only disease not amenable to fresh biopsy may be eligible in consultation with the Sponsor.

• Acceptable laboratory parameters and adequate organ reserve.

Locations
United States
Illinois
University of Chicago Medical Center
Chicago
Massachusetts
Beth Israel Deaconess Medical Center
Boston
Dana Farber Cancer Institute
Boston
Massachusetts General Hospital
Boston
Michigan
START Midwest
Grand Rapids
Nebraska
Oncology Hematology West p.c. dba Nebraska Cancer Specialists
Grand Island
Nebraska Cancer Specialists
Omaha
Oregon
Providence Portland Medical Center
Portland
Pennsylvania
UPMC Hillman Cancer Center
Camp Hill
UPMC Hillman Cancer Center
Carlisle
UPMC Hillman Cancer Center
Erie
UPMC Pinnacle - Community Osteopathic Medical Sciences Pavilion (MSP)
Harrisburg
UPMC Pinnacle Harrisburg
Harrisburg
UPMC Pinnacle - Ortenzio Cancer Center (OCC)
Mechanicsburg
UPMC Hillman Cancer Center
Pittsburgh
UPMC Hillman Cancer Center at UPMC Memorial
York
Tennessee
The Sarah Cannon Research Institute / Tennessee Oncology
Nashville
Other Locations
Bulgaria
Complex Oncology Center - Burgas EOOD, Department of Medical Oncology
Burgas
Multiprofile Hospital for Active Treatment-Uni Hospital
Panagyurishte
Multiprofile Hospital for Active Treatment Heart and Brain EAD, Clinic of Medical Oncology
Pleven
Complex Oncology Center - Ruse EOOD
Ruse
University Mulitprofile Hospital for Active Treatment Sv. Ivan Rilski
Sofia
Poland
University Clinical Centre, Early Clinical Trials Unit
Gdańsk
Pratia MCM Krakow
Kraków
Europejskie Centrum Zdrowia Otwock
Otwock
Med-Polonia Sp. z.o.o.
Poznań
LUX MED Onkologia Sp. z.o.o.
Warszawa
Narodowy Instytut Onkologii im
Warszawa
Mazovian Onkological Hospital
Wieliszew
Spain
ICO Badalona / Hospital Universitari Germans Trias i Pujol
Badalona
Hospital Ruber Internacional
Madrid
Hospital Universitario La Princesa
Madrid
Ukraine
Communal Non-profit Enterprise City Clinical Hospital #4 of Dnipro
Dnipro
Communal Non-Profit Enterprise Regional Center of Oncology, Oncosurgical Department of Head and Neck
Kharkiv
Communal Nonprofit Enterprise Regional Clinical Oncology Center of Kirovohrad Regional Council
Kirovohrad
Kyiv City Clinical Oncological Centre
Kyiv
National Cancer Institute of Ukraine
Kyiv
Sumy Clinical Oncological Hospital
Sumy
Communal Nonprofit Enterprise Podilsky Regional Center of Oncology
Vinnytsia
Time Frame
Start Date: 2018-12-12
Completion Date: 2025-01
Participants
Target number of participants: 162
Treatments
Experimental: Cohort 1
0.03 mg/kg administered IV every 3 weeks.
Experimental: Cohort 2
0.1 mg/kg administered IV every 3 weeks.
Experimental: Cohort 3
0.3 mg/kg administered IV every 3 weeks.
Experimental: Cohort 4
1.0 mg/kg administered IV every 3 weeks.
Experimental: Cohort 5
30. mg/kg administered IV every 3 weeks.
Experimental: Cohort 6
6.0 mg/kg administered IV every 3 weeks.
Experimental: Cohort 7
10.0 mg/kg administered IV every 3 weeks.
Related Therapeutic Areas
Sponsors
Leads: MacroGenics

This content was sourced from clinicaltrials.gov

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