MGC018 With or Without MGA012 in Advanced Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03729596 |
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Recruitment Status :
Active, not recruiting
First Posted : November 2, 2018
Last Update Posted : November 17, 2022
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Sponsor:
MacroGenics
Information provided by (Responsible Party):
MacroGenics
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Brief Summary:
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Squamous Cell Carcinoma of Head and Neck Triple Negative Breast Cancer Melanoma Advanced Solid Tumor, Adult Metastatic Castrate Resistant Prostate Cancer Non Small Cell Lung Cancer | Biological: vobramitamab duocarmazine Biological: retifanlimab | Phase 1 Phase 2 |
This Phase 1/2 study will characterize safety, dose-limiting toxicities (DLTs), and maximum tolerated/administered dose (MTD/MAD) and anti-tumor activity for vobramitamab duocarmazine as monotherapy (Module A) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.
Module B, vobramitamab duocarmazine in combination with retifanlimab will not enroll.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors |
| Actual Study Start Date : | November 21, 2018 |
| Estimated Primary Completion Date : | March 2023 |
| Estimated Study Completion Date : | May 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1
0.5 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: Cohort 2
1.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: Cohort 3
2.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: Cohort 4
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: Cohort 5
4.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: mCRPC expansion
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: NSCLC expansion
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: TNBC expansion
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: Melanoma expansion
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: SCCHN expansion
3.0 mg/kg IV every 3 weeks
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 |
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Experimental: vobramitamab duocarmazine plus retifanlimab
vobramitamab duocarmazine: Anti-B7-H3 antibody drug conjugate; retifanlimab: Anti-PD-1 antibody
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Biological: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate
Other Name: MGC018 Biological: retifanlimab Anti-PD-1 Antibody
Other Names:
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Primary Outcome Measures :
- Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03 [ Time Frame: Throughout the study up to 24 months ]Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
- Number of patients with dose limiting toxicities (DLT) [ Time Frame: up to 42 days from first dose ]Maximum tolerated or maximum administered dose of vobramitamab duocarmazine
Secondary Outcome Measures :
- Best overall response (BOR) of vobramitamab duocarmazine [ Time Frame: Throughout the study for up to 24 months ]The best response recorded from the start of the study treatment until the end of treatment with vobramitamab duocarmazine, taking into account any requirement for confirmation of response.
- Objective response rate (ORR) of vobramitamab duocarmazine [ Time Frame: Efficacy evaluations every 9 weeks throughout the study for up to 24 months ]The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine
- Progression free survival (PFS) of vobramitamab duocarmazine [ Time Frame: Every 9 weeks for up to 24 months ]Efficacy assessed as the first dose date to the date of first documented progression using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first.
- Duration of response (DoR) of vobramitamab duocarmazine [ Time Frame: Throughout the study for up to 48 months ]Efficacy assessed as the time from the date of initial objective response to the date of first documented progression RECIST v1.1, or the date of death from any cause, whichever occurs first.
- Overall survival (OS) of vobramitamab duocarmazine [ Time Frame: Every 9 weeks for up to 24 months ]Efficacy assessed as the time from the first dose date to the date of death from any cause.
- PSA response rate [ Time Frame: Every 3 weeks up to 24 months ]Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later
- Best PSA response [ Time Frame: Every 3 weeks up to 24 months ]For prostate cancer patients, the greatest change from baseline in PSA.
- Radiographic progression-free survival [ Time Frame: Every 9 weeks for up to 24 months ]For prostate cancer patients, time from first dose to first radiographic progression using the Prostate Cancer Working Group criteria, or death from any cause, whichever occurs first.
- Area under the curve [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Area under the plasma concentration versus time curve of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- Cmax [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Maximum Plasma Concentration of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- Tmax [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- Ctrough [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Trough plasma concentration of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- CL [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- Vss [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months ]Apparent volume of distribution at steady state of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- t1/2 [ Time Frame: Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months . ]Terminal half life of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
- Immunogenicity [ Time Frame: Every 3 weeks through end of treatment, up to 24 months ]Percent of patients with anti-drug antibodies against vobramitamab duocarmazine and retifanlimab
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:
- Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
- Eastern Cooperative Oncology Group performance status of ≤2
- Life expectancy ≥ 12 weeks for dose escalation phase and ≥ 24 weeks for cohort expansion phase
- Measurable disease. Prostate cancer patients with bone only disease are eligible.
- Acceptable laboratory parameters and adequate organ reserve.
- Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical benefit is available.
Module A Cohort Expansion:
- mCRPC that has progressed with one prior line of chemotherapy for metastatic disease and no more than two prior lines of anti-hormonal therapy.
- NSCLC: metastatic disease after standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than 2 prior lines of chemotherapy.
- TNBC: Locally advance or metastatic disease that has progressed following at least one systemic therapy.
- SCCHN that has progressed during or following at least one systemic therapy for metastatic or recurrent unresectable disease. No more than 2 prior lines of chemotherapy.
- Melanoma that has progressed during or following at least one systemic treatment for unresectable locally advanced or metastatic disease. Patients who are intolerant of or refused standard therapy are eligible.
Exclusion Criteria:
- Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on MRI, CT or PET within 6 months, or history of leptomeningeal disease or cord compression at the time of enrollment.
- Prior treatment with B7-H3 targeted agents for cancer.
- Treatment with systemic cancer therapy, biologic agents, or anti-hormonal therapy (mCRPC) within 4 weeks, prior small molecule targeted or kinase inhibitors within 14 days or 5 half-lives, prior radioligand within 6 months
- Clinically significant cardiovascular disease.
- Clinically significant pulmonary compromise or requirement for supplemental oxygen.
- History of clinically-significant cardiovascular disease, including but not limited to pericarditis or pericardial effusion.
- Active viral (including confirmed or presumed COVID-19), bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration.
- Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
- Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- Major trauma or major surgery within 4 weeks of first study drug administration.
- Clinically significant venous insufficiency.
- > Grade 1 peripheral neuropathy.
- Evidence of pleural effusion.
- Evidence of ascites.
- Serum testosterone >50 ng/dl or >1.7 nmol/L in mCRPC in Module A Cohort Expansion Phase
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): NCT03729596
Locations
Show 21 study locations
Sponsors and Collaborators
MacroGenics
Investigators
| Study Director: | Ashley Ward, M.D. | MacroGenics |
| Responsible Party: | MacroGenics |
| ClinicalTrials.gov Identifier: | NCT03729596 |
| Other Study ID Numbers: |
CP-MGC018-01 |
| First Posted: | November 2, 2018 Key Record Dates |
| Last Update Posted: | November 17, 2022 |
| Last Verified: | November 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 |
Keywords provided by MacroGenics:
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antibody-drug conjugate (ADC) B7-H3 |
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms Squamous Cell Carcinoma of Head and Neck Neoplasms by Site Neoplasms Neoplasms by Histologic Type Carcinoma, Squamous Cell |
Carcinoma Neoplasms, Glandular and Epithelial Breast Neoplasms Breast Diseases Skin Diseases Head and Neck Neoplasms |