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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05293496
• Other study ID #: CP-MGC018-02
• Status: Recruiting
• Phase: Phase 1
• Start date: April 19, 2022
• Est. completion date: March 2026

Study information

• Verified date: March 2024
• Source: MacroGenics
• Contact: Global Trial Manager
• Phone: 301-251-5172
• Email: info[@]macrogenics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 278
• Est. completion date: March 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• vobramitamab duocarmazine
Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.
• lorigerlimab
Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Virginia Comprehensive Cancer Center	Charlottesville	Virginia
United States	Carolina BioOncology	Huntersville	North Carolina
United States	University of California, Los Angeles	Los Angeles	California
United States	Weill Cornell Medicine	New York	New York
United States	Stephenson Cancer Center, The University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Pittsburgh Medical Center, Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Florida Cancer Specialists and Research Institute	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)		Up to 2 years
Primary	Number of participants with serious adverse events (SAEs)		Up to 2 years
Primary	Number of participants with AEs leading to study treatment discontinuation		Up to 2 years
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Number of participants who develop anti-drug antibodies (ADA) to vobramitamab duocarmazine		Assessed every 4 weeks up to 2 years
Secondary	Number of participants who develop ADA to lorigerlimab		Assessed every 4 weeks up to 2 years
Secondary	Objective response rate (ORR)		Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.