Clinical Trials /

MGC018 With or Without MGA012 in Advanced Solid Tumors

NCT03729596

Description:

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in combination with MGA012 in patients with advanced solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MGC018 With or Without MGA012 in Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CP-MGC018-01
  • NCT ID: NCT03729596

Conditions

  • Advanced Solid Tumor, Adult
  • Metastatic Castrate Resistant Prostate Cancer
  • Non Small Cell Lung Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
MGC018MGC018 Monotherapy
MGA012INCMGA00012MGC018 plus MGA012

Purpose

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in combination with MGA012 in patients with advanced solid tumors.

Detailed Description

      This Phase 1/2 study will characterize safety, dose-limiting toxicities (DLTs), and maximum
      tolerated/administered dose (MTD/MAD) and anti-tumor activity for MGC018 as monotherapy
      (Module A) in patients with advanced solid tumors. Each module consists of a Dose Escalation
      (3+3+3 design) followed by a Cohort Expansion Phase. 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), and
      triple-negative breast cancer (TNBC). 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, MGC018 in combination with MGA012, Dose Escalation and Cohort Expansion will
      commence only upon sponsor notification to all study investigators.
    

Trial Arms

NameTypeDescriptionInterventions
MGC018 MonotherapyExperimentalMGC018: Anti-B7-H3 antibody drug conjugate
  • MGC018
MGC018 plus MGA012ExperimentalMGC018: Anti-B7-H3 antibody drug conjugate; MGA012: Anti-PD-1 antibody
  • MGC018
  • MGA012

Eligibility 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.

        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.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events of MGC018 and MGC018 + MGA012 as assessed by CTCAE v4.03
Time Frame:30 days after last dose
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Preliminary anti-tumor activity of MGC018 and MGC018+MGA012
Time Frame:24 months
Safety Issue:
Description:Efficacy assessed as best overall response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Measure:PSA response rate
Time Frame:24 months
Safety Issue:
Description:Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA)
Measure:Radiographic progression-free survival
Time Frame:24 months
Safety Issue:
Description:For prostate cancer patients, time from first dose to first radiographic progression in soft tissue or bone, or death from any cause
Measure:Patient-reported Outcome
Time Frame:24 months
Safety Issue:
Description:For prostate cancer patients, change from baseline in pain intensity as measured by the Brief Pain Inventory-Short Form scale
Measure:Area under the curve
Time Frame:24 months
Safety Issue:
Description:Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012
Measure:Cmax
Time Frame:24 months
Safety Issue:
Description:Maximum Plasma Concentration of MGC018 and MGC018+MGA012
Measure:Tmax
Time Frame:24 months
Safety Issue:
Description:Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+MGA012
Measure:Ctrough
Time Frame:24 months
Safety Issue:
Description:Trough plasma concentration of MGC018 and MGC018+MGA012
Measure:CL
Time Frame:24 months
Safety Issue:
Description:Total body clearance of the drug from plasma of MGC018 and MGC018+MGA012
Measure:Vss
Time Frame:24 months
Safety Issue:
Description:Apparent volume of distribution at steady state of MGC018 and MGC018+MGA012
Measure:t1/2
Time Frame:24 months
Safety Issue:
Description:Terminal half life of MGC018 and MGC018+MGA012
Measure:Immunogenicity
Time Frame:24 months
Safety Issue:
Description:Percent of patients with anti-drug antibodies against MGC018 and MGA012

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MacroGenics

Trial Keywords

  • antibody-drug conjugate (ADC)
  • B7-H3
  • Prostate cancer

Last Updated

August 27, 2020