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

• ClinicalTrials.gov Identifier: NCT05293496
• Recruitment Status: Recruiting
• First Posted: March 24, 2022
• Last Update Posted: May 24, 2022
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Study Description

Brief Summary:

Study CP-MGC018-02 is a study of MGC018 in combination with lorigerlimab. 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 mCRPC, melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled.

MGC018 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 a total of 35 cycles (approximately 2 years).

Tumor assessments are performed every 8 weeks 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. .

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Castration-Resistant Prostatic Cancer; Malignant Melanoma; Pancreatic Ductal Carcinoma; Hepatocellular Cancer; Epithelial Ovarian Cancer; Renal Cell Carcinoma	Biological: MGC018; Biological: lorigerlimab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 258 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 19, 2022
• Estimated Primary Completion Date: March 2024
• Estimated Study Completion Date: March 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: MGC018 at dose level 1 and checkpoint inhibitor intravenously (IV) every 4 weeks	Biological: MGC018; MGC018 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.; Other Name: MGD019
Experimental: Cohort 2; MGC018 at dose level 2 and checkpoint inhibitor IV every 4 weeks	Biological: MGC018; MGC018 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.; Other Name: MGD019
Experimental: Cohort 3; MGC018 at dose level 3 and checkpoint inhibitor IV every 4 weeks	Biological: MGC018; MGC018 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.; Other Name: MGD019
Experimental: Cohort Expansion; Maximum tolerated dose of MGC018 and checkpoint inhibitor IV every 4 weeks	Biological: MGC018; MGC018 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.; Other Name: MGD019

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs) [ Time Frame: Up to 2 years ]
2. Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
3. Number of participants with AEs leading to study treatment discontinuation [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :

1. Maximum concentration of MGC018 [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
   Highest concentration of MGC018 at the end of infusion
2. Maximum concentration of lorigerlimab [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
   Highest concentration of MGC018 at the end of infusion
3. Time to maximum concentration of MGC018 [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
4. Time to maximum concentration of lorigerlimab [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
5. Area under the concentration-time curve to time t (AUCt) of MGC018 [ Time Frame: Cycle 1 Study Days 1, 8, 15 and Cycle 2 Day 1 ]
   Average drug concentration from time zero to the time of last measurable concentration in a 3-week dosing interval
6. AUCt of lorigerlimab [ Time Frame: Cycle 1 Study Days 1, 8, 15 and Cycle 2 Day 1 ]
   Average drug concentration from time zero to the time of last measurable concentration in a 3-week dosing interval
7. AUCtau of MGC018 [ Time Frame: Study Days 1, 8, 15, in Cycle 1 and Day 1 in Cycle 2 ]
   Average drug concentration during the 3-week dosing interval
8. AUCtau of lorigerlimab [ Time Frame: Study Days 1, 8, 15, in Cycle 1 and Day 1 in Cycle 2 ]
   Average drug concentration during the 3-week dosing interval
9. Trough concentration of MGC018 [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
   The amount of MGC018 left after dosing
10. Trough concentration of lorigerlimab [ Time Frame: Day 1 of each cycle (every three weeks) up to 2 years. ]
    The amount of MGC018 left after dosing
11. Number of participants who develop anti-drug antibodies (ADA) to MGC018 [ Time Frame: Assessed every 3 weeks up to 2 years ]
12. Number of participants who develop ADA to lorigerlimab [ Time Frame: Assessed every 3 weeks up to 2 years ]
13. Objective response rate (ORR) [ Time Frame: Assessed every 6 weeks for the first 6 months, then every 12 weeks for up to 3 years. ]
14. Progression free survival (PFS) [ Time Frame: 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 3 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.
15. Duration of response (DoR) [ Time Frame: 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.
16. Overall survival (OS) [ Time Frame: 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.
17. Radiographic PFS (rPFS) for mCRPC [ Time Frame: 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
18. Prostate-specific antigen (PSA) response rate for mCRPC [ Time Frame: PSA is assessed every 3 weeks, up to 2 years ]
    PSA response is defined as ≥ 50% decline from baseline in PSA with confirmation at least 3 weeks later.
19. Best PSA percent change for mCRPC [ Time Frame: PSA is assessed every 3 weeks, up to 2 years ]
20. PSA progression for mCRPC [ Time Frame: PSA is assessed every 3 weeks, up to 2 years ]
    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.
21. Duration of PSA response for mCRPC [ Time Frame: PSA is assessed every 3 weeks, up to 2 years ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 tumor including 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 with minimal drug-drug interactions or overlapping toxicity of the antiretroviral therapy study treatments.
• 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.
• Pleural effusion or ascites. Trace pleural or peritoneal fluid is not exclusionary.

Contacts and Locations

Contacts

Contact: Global Trial Manager; 301-251-5172; info@macrogenics.com

Locations

United States, California

University of California, Los Angeles; Not yet recruiting

Los Angeles, California, United States, 90095

United States, Florida

Florida Cancer Specialists and Research Institute; Not yet recruiting

Sarasota, Florida, United States, 34232

United States, Maryland

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center; Recruiting

Baltimore, Maryland, United States, 21287

United States, North Carolina

Carolina BioOncology; Recruiting

Huntersville, North Carolina, United States, 28078

United States, Oklahoma

Stephenson Cancer Center, The University of Oklahoma; Not yet recruiting

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

University of Pittsburgh Medical Center, Hillman Cancer Center; Not yet recruiting

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

MacroGenics

Investigators

• Study Director: Stephen L. Eck, M.D.; MacroGenics

More Information

• Responsible Party: MacroGenics
• ClinicalTrials.gov Identifier: NCT05293496
• Other Study ID Numbers: CP-MGC018-02
• First Posted: March 24, 2022
• Last Update Posted: May 24, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Melanoma; Carcinoma, Ovarian Epithelial; Carcinoma, Ductal; Liver Neoplasms; Carcinoma, Hepatocellular; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Carcinoma, Pancreatic Ductal; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary; Digestive System Neoplasms; Digestive System Diseases