A Study Of MGC018 In Combination With MGD019 In Participants With Advanced Solid Tumors

Study Overview

A Study of MGC018 in Combination With MGD019 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. .

N/A

Advanced Solid Tumor
Castration-Resistant Prostatic Cancer
Malignant Melanoma
Pancreatic Ductal Carcinoma
Hepatocellular Cancer
Epithelial Ovarian Cancer
Renal Cell Carcinoma

BIOLOGICAL: vobramitamab duocarmazine
BIOLOGICAL: lorigerlimab

CP-MGC018-02

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-02-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-07-25
First Submitted that Met QC Criteria 2022-03-14	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-07-28
First Posted (ACTUAL) 2022-03-24	Results First Posted N/A	Last Verified 2025-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
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. BIOLOGICAL: lorigerlimab Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.

Primary Outcome Measures	Measure Description	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	Measure Description	Time Frame
Mean maximum observed concentration (Cmax) of vobramitamab duocarmazine	Peak concentration of vobramitamab duocarmazine	Throughout the study, up to 2 years
Mean maximum observed concentration (Cmax) of lorigerlimab	Peak concentration of lorigerlimab	Throughout the study, up to 2 years
Mean time to maximum concentration (Tmax) of vobramitamab duocarmazine	Time at which peak concentration of vobramitamab duocarmazine is observed	Throughout the study, up to 2 years
Mean time to maximum concentration (Tmax) of lorigerlimab	Time at which peak concentration of lorigerlimab is observed	Throughout the study, up to 2 years
Mean 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	Throughout the study, up to 2 years
Mean 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	Throughout the study, up to 2 years
Mean 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.
Mean trough concentration of lorigerlimab	Concentration of lorigerlimab at the end of a dosing interval	Throughout the study, up to 2 years
Number of participants who develop anti-drug antibodies (ADA) to vobramitamab duocarmazine		Throughout the study, up to 2 years
Number of participants who develop ADA to lorigerlimab		Throughout the study, 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.
Median 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.
Median 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.
Median 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
Median 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 from baseline 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.
Median time to 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.
Median 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.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Denise Casey, M.D., MacroGenics

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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