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

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

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

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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


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




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.



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05293496


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

Locations
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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
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Study Director: Stephen L. Eck, M.D. MacroGenics
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Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT05293496    
Other Study ID Numbers: CP-MGC018-02
First Posted: March 24, 2022    Key Record Dates
Last Update Posted: May 24, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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