Advanced Solid Tumor, Castration-Resistant Prostatic Cancer, Epithelial Ovarian Cancer, Hepatocellular Cancer, Malignant Melanoma, Pancreatic Ductal Carcinoma, Renal Cell Carcinoma
Conditions
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. .
Interventions
BIOLOGICALvobramitamab duocarmazine
Vobramitamab duocarmazine is an antibody drug conjugate (ADC) targeted against B7-H3.
BIOLOGICALlorigerlimab
Lorigerlimab is a bispecific DART® molecule that binds PD-1 and CTLA-4.
Sponsors
MacroGenics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Mean time to maximum concentration (Tmax) of lorigerlimab | Throughout the study, up to 2 years | Time at which peak concentration of lorigerlimab is observed |
| Mean area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine | Throughout the study, up to 2 years | Concentration of vobramitamab duocarmazine in the bloodstream during the 28-day dosing interval after dose administration |
| Mean area under the concentration-time curve during the dosing interval (AUCtau) of lorigerlimab | Throughout the study, up to 2 years | Concentration of lorigerlimab in the bloodstream during the 28-day dosing interval after dose administration |
| Mean trough concentration of vobramitamab duocarmazine | Day 1 of each cycle (every 4 weeks) up to 2 years. | Concentration of vobramitamab duocarmazine at the end of a dosing interval |
| Mean trough concentration of lorigerlimab | Throughout the study, up to 2 years | Concentration of lorigerlimab at the end of a dosing interval |
| 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. | — |
| Mean maximum observed concentration (Cmax) of vobramitamab duocarmazine | Throughout the study, up to 2 years | Peak concentration of vobramitamab duocarmazine |
| Median duration of response (DoR) | Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years. | 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. |
| Median overall survival (OS) | 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 | OS is defined as the time from the first dose date to the date of death from any cause. |
| Median radiographic PFS (rPFS) for mCRPC | Assessed every 8 weeks for the first 6 months, then every 12 weeks for up to 2 years. | 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 |
| Prostate-specific antigen (PSA) response rate 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 response is defined as ≥ 50% decline from baseline in PSA with confirmation at least 3 weeks later. |
| 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 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 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. |
| Median duration of PSA response 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. | 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. |
| Median progression free survival (PFS) | 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. | 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. |
| Mean maximum observed concentration (Cmax) of lorigerlimab | Throughout the study, up to 2 years | Peak concentration of lorigerlimab |
| Mean time to maximum concentration (Tmax) of vobramitamab duocarmazine | Throughout the study, up to 2 years | Time at which peak concentration of vobramitamab duocarmazine is observed |
Countries
United States
Outcome results
None listed