Clinical trial NCT05293496: A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Castration-Resistant Prostatic Cancer
Malignant Melanoma
Pancreatic Ductal Carcinoma
Hepatocellular Cancer
Epithelial Ovarian Cancer
Renal Cell Carcinoma
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2022-03-24
Enrollment: 278
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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. .


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 2 years
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to 2 years
measure: Number of participants with AEs leading to study treatment discontinuation
timeFrame: Up to 2 years
Secondary outcomes:
measure: Mean maximum observed concentration (Cmax) of vobramitamab duocarmazine
timeFrame: Throughout the study, up to 2 years
measure: Mean maximum observed concentration (Cmax) of lorigerlimab
timeFrame: Throughout the study, up to 2 years
measure: Mean time to maximum concentration (Tmax) of vobramitamab duocarmazine
timeFrame: Throughout the study, up to 2 years
measure: Mean time to maximum concentration (Tmax) of lorigerlimab
timeFrame: Throughout the study, up to 2 years
measure: Mean area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine
timeFrame: Throughout the study, up to 2 years
measure: Mean area under the concentration-time curve during the dosing interval (AUCtau) of lorigerlimab
timeFrame: Throughout the study, up to 2 years
measure: Mean trough concentration of vobramitamab duocarmazine
timeFrame: Day 1 of each cycle (every 4 weeks) up to 2 years.
measure: Mean trough concentration of lorigerlimab
timeFrame: Throughout the study, up to 2 years
measure: Number of participants who develop anti-drug antibodies (ADA) to vobramitamab duocarmazine
timeFrame: Throughout the study, up to 2 years
measure: Number of participants who develop ADA to lorigerlimab
timeFrame: Throughout the study, up to 2 years
measure: Objective response rate (ORR)
timeFrame: Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
measure: Median progression free survival (PFS)
timeFrame: 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.
measure: Median duration of response (DoR)
timeFrame: Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
measure: Median overall survival (OS)
timeFrame: 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
measure: Median radiographic PFS (rPFS) for mCRPC
timeFrame: Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years.
measure: Prostate-specific antigen (PSA) response rate for mCRPC
timeFrame: 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.
measure: Best PSA percent change from baseline for mCRPC
timeFrame: 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.
measure: Median time to PSA progression for mCRPC
timeFrame: 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.
measure: Median duration of PSA response for mCRPC
timeFrame: 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.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology
state: North Carolina
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center, The University of Oklahoma
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Hillman Cancer Center
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
Study officials:
affiliation: MacroGenics
name: Denise Casey, M.D.
role: STUDY_DIRECTOR
References: