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

NCT05293496 | Completed Phase 1 FDA Drug

• 1 other identifier: CP-MGC018-02
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

Brief Summary

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. .

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (19)

• Mean maximum observed concentration (Cmax) of vobramitamab duocarmazine

  Throughout the study, up to 2 years

• Mean maximum observed concentration (Cmax) of lorigerlimab

  Throughout the study, up to 2 years

• Mean time to maximum concentration (Tmax) of vobramitamab duocarmazine

  Throughout the study, up to 2 years

• Mean time to maximum concentration (Tmax) of lorigerlimab

  Throughout the study, up to 2 years

• Mean area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine

  Throughout the study, up to 2 years

Study Arms (7)

Cohort -1

EXPERIMENTAL

vobramitamab duocarmazine at dose level -1 and lorigerlimab intravenously (IV) every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort 1

EXPERIMENTAL

vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort 2

EXPERIMENTAL

vobramitamab duocarmazine at dose level 1 and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort 3

EXPERIMENTAL

vobramitamab duocarmazine at dose level 2 and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort 4

EXPERIMENTAL

vobramitamab duocarmazine at dose level 3 and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort 5

EXPERIMENTAL

vobramitamab duocarmazine at dose level 4 and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Cohort Expansion

EXPERIMENTAL

maximum tolerated dose of vobramitamab duocarmazine and lorigerlimab IV every 4 weeks

Biological: vobramitamab duocarmazine; Biological: lorigerlimab

Interventions

vobramitamab duocarmazine BIOLOGICAL

Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.

Also known as: MGC018

Cohort -1; Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort Expansion

lorigerlimab BIOLOGICAL

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

Also known as: MGD019

Cohort -1; Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• 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.
• History of Guillain-Barre syndrome, myasthenia gravis, or other autoimmune sensory or motor neuropathies.

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (10)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Florida Cancer Specialists and Research Institute

Sarasota, Florida, 34232, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

Location

Stephenson Cancer Center, The University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh Medical Center, Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Melanoma; Carcinoma, Pancreatic Ductal; Liver Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Liver Diseases; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Gonadal Disorders; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases

Study Officials

• Denise Casey, M.D.

  MacroGenics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2022
• First Posted: March 24, 2022
• Study Start: April 19, 2022
• Primary Completion: June 24, 2025
• Study Completion: August 26, 2025
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)