A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors

A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors

Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab (MGD019). The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, metastatic castration-resistant prostate cancer (mCRPC), melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled.

Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years.

Tumor assessments are performed every 8 weeks (± 7 days) for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD).

Participants will be followed for safety throughout the study. .

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma; Advanced Solid Tumor; Epithelial Ovarian Cancer; Hepatocellular Cancer; Malignant Melanoma; Pancreatic Ductal Carcinoma; Castration-Resistant Prostatic Cancer
• Intervention / Treatment: Biological: vobramitamab duocarmazine; Biological: lorigerlimab

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Global Trial Manager; Phone Number: 301-251-5172; Email: info@macrogenics.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Principal Investigator: Bartosz Chmielowski, MD
    • San Francisco, California, United States, 94158
      • Not yet recruiting
      • University of California, San Francisco
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists and Research Institute
      • Principal Investigator: Manish Patel, MD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Winship Cancer Institute of Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Eugene Shenderov
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Principal Investigator: Jones Nauseef, MD
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology
      • Principal Investigator: John Powderly, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Stephenson Cancer Center, The University of Oklahoma
      • Principal Investigator: Susanna Ulahannan, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center, Hillman Cancer Center
      • Principal Investigator: Jason Luke, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Comprehensive Cancer Center
      • Principal Investigator: Matthew Reilley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Ability to provide and document informed consent and willing and able to comply with all study procedures.
• Participants diagnosed with advanced solid tumors including but not limited to metastatic castration-resistant prostate cancer, melanoma, pancreatic cancer, hepatocellular carcinoma, ovarian cancer and renal cell carcinoma.
• Participants have received approved therapies according to their diagnosis.
• Participants must have an available tumor tissue sample. A fresh tumor biopsy may be performed if no archival sample is available.
• Eastern Cooperative Oncology Group performance status of less than or equal to 2.
• Life expectancy of at least 12 weeks.
• Evidence of measurable tumor for evaluation
• Acceptable end organ function according to laboratory results.
• Patients must agree to use highly-effective contraception during the study, and not donate sperm or ova.

Exclusion Criteria:

• Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
• Another malignancy that required treatment within the past 2 years. Participants who have had curative therapy for non-melanomatous skin cancer, localized prostate cancer (Gleason score < 6), or carcinoma in situ are eligible for the study.
• Active viral, bacterial, or fungal infection requiring systemic treatment within 1 week of initiation of study drug. Participants are eligible after SARS CoV 2-related symptoms have fully recovered for ≥ 72 hours.
• History of immunodeficiency. Participants with HIV are eligible if they have a CD4+ count ≥ 300/µL, undetectable viral load, and maintained on antiretroviral therapy for a minimum of 4 weeks.
• Prior autologous/allogeneic stem cell or tissue/solid organ transplant
• Prior treatment with MGD009, enoblituzumab, or other B7-H3 targeted agents for cancer.
• Clinically significant cardiovascular disease, lung compromise, venous insufficiency, or gastrointestinal disorders.
• Participants with greater than Grade 1 peripheral neuropathy.
• Participants who have a history of severe adverse events (AEs) from immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or CTLA-4 inhibitors). All other AEs from prior immune checkpoint inhibitors must be resolved to Grade 1 or less. Participants with any grade neurologic toxicity from prior immune checkpoint inhibitors are excluded.
• Pleural effusion or ascites. Trace pleural or peritoneal fluid is not exclusionary.
• History of Guillain-Barre syndrome, myasthenia gravis, or other autoimmune sensory or motor neuropathies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort -1; vobramitamab duocarmazine at dose level -1 and lorigerlimab intravenously (IV) every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort 1; vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort 2; vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort 3; vobramitamab duocarmazine at dose level 2 and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort 4; vobramitamab duocarmazine at dose level 3 and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort 5; vobramitamab duocarmazine at dose level 4 and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019
Experimental: Cohort Expansion; maximum tolerated dose of vobramitamab duocarmazine and lorigerlimab IV every 4 weeks	Biological: vobramitamab duocarmazine; Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.; Other Names: MGC018; Biological: lorigerlimab; Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.; Other Names: MGD019

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events (AEs)	Up to 2 years
Number of participants with serious adverse events (SAEs)	Up to 2 years
Number of participants with AEs leading to study treatment discontinuation	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax) of vobramitamab duocarmazine	Peak concentration of vobramitamab duocarmazine	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8; Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years
Maximum observed concentration (Cmax) of lorigerlimab	Peak concentration of lorigerlimab	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hour and 4 hours after EOI, Day 8, Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years
Time to maximum concentration (Tmax) of vobramitamab duocarmazine	Time at which peak concentration of vobramitamab duocarmazine is observed	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.
Time to maximum concentration (Tmax) of lorigerlimab	Time at which peak concentration of lorigerlimab is observed	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hour and 4 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.
Area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine	Concentration of vobramitamab duocarmazine in the bloodstream during the 28-day dosing interval after dose administration	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour)], 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.
Area under the concentration-time curve during the dosing interval (AUCtau) of lorigerlimab	Concentration of lorigerlimab in the bloodstream during the 28-day dosing interval after dose administration	Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hours and 4 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.
Trough concentration of vobramitamab duocarmazine	Concentration of vobramitamab duocarmazine at the end of a dosing interval	Day 1 of each cycle (every 4 weeks) up to 2 years.
Trough concentration of lorigerlimab	Concentration of lorigerlimab at the end of a dosing interval	Day 1 of each cycle (every 4 weeks) up to 2 years.
Number of participants who develop anti-drug antibodies (ADA) to vobramitamab duocarmazine		Assessed every 4 weeks up to 2 years
Number of participants who develop ADA to lorigerlimab		Assessed every 4 weeks up to 2 years
Objective response rate (ORR)		Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
Progression free survival (PFS)	PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.	Assessed every 8 weeks for the first 6 months, then every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years.
Duration of response (DoR)	DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first.	Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
Overall survival (OS)	OS is defined as the time from the first dose date to the date of death from any cause.	Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years
Radiographic PFS (rPFS) for mCRPC	rPFS is defined as the time from the first dose of study drug to the first occurrence of radiographic PD of soft tissue lesions using RECIST v1.1, or appearance of ≥ 2 new bone lesions, or death from any cause	Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
Prostate-specific antigen (PSA) response rate for mCRPC	PSA response is defined as ≥ 50% decline from baseline in PSA with confirmation at least 3 weeks later.	PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.
Best PSA percent change for mCRPC		PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.
PSA progression for mCRPC	PSA progression is defined as an increase that is ≥ 25% and ≥ 2 ng/mL the baseline or lowest value observed, and which confirmed by a second value at least 3 weeks later.	PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.
Duration of PSA response for mCRPC	DoR of PSA is defined as the time from the date of initial PSA response to the date of first documented PSA progression or death from any cause, whichever occurs first.	PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.

Collaborators and Investigators

• Sponsor: MacroGenics
• Investigators: Study Director: Denise Casey, M.D., MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 12, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Liver Diseases; Prostatic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Ovarian Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Skin Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Genital Diseases, Female; Prostatic Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Melanoma; Carcinoma, Ovarian Epithelial; Liver Neoplasms; Prostatic Neoplasms, Castration-Resistant; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: CP-MGC018-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No