Advanced Hepatocellular Carcinoma (HCC)Phase 1/2NCT04212221

MGD013 Monotherapy and Combination With Brivanib Dose Escalation and Expansion Study in Advanced Liver Cancer Patients

A Phase 1/2 study testing MGD013 monotherapy and MGD013 in combination with Brivanib Alaninate in people with Advanced Hepatocellular Carcinoma (HCC), run by Zai Lab (Shanghai) Co., Ltd. at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Advanced Hepatocellular Carcinoma (HCC)
What is being tested?: MGD013 monotherapy and MGD013 in combination with Brivanib Alaninate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 89 participants
Where: 1 siteChina
Study dates: 20 Apr 2020to 27 Apr 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects who voluntarily sign the informed consent form (ICF);
Male or female subjects who are aged 18-75 years old;
Subjects with histologic, cytologic or clinical confirmed diagnosis of advanced HCC (Phase I could include intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma), and are not suitable for surgery or loco-regional therapy or have progressed following surgery and/or loco-regional therapy;
Subject who has at least one measurable lesion according to RECIST v1.1 criteria.
Phase I study: subjects who have previously received at least one line of systemic therapy, including immune checkpoint inhibitors, molecular targeted drugs or systematic chemotherapy, alone or in combination, and failed (progression confirmed by imaging) or were intolerant at the discretion of investigator; PhaseII：Advanced HCC cohort with subjects who have previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) prior one line immune checkpoint inhibitor treatment, including anti-PD-1 antibody/anti-PD-L1 antibody and / or anti-CTLA-4 antibody, and/or molecular targeted therapy or systematic chemotherapy (monotherapy or in combination); Phase II: Advanced HCC cohort with subjects who have not previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) or were intolerant to (at the discretion of investigator) previous molecular targeted therapy or systematic chemotherapy, without receiving immune checkpoint inhibitor treatment (including anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, and bispecific antibodies including the above targets).
Previous anti-tumor therapy must be completed no less than 2 weeks prior to the study treatment and all adverse events related to previous treatment must have recovered to CTCAE Grade ≤1; if subjects who have received prior immune checkpoint inhibitors have immune-related endocrinopathy, it should be controlled with hormone replacement therapy.

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Phase I: Child-Pugh Class A; Phase II: Child-Pugh Class A or B with a score of ≤ 7;
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
Subjects with life expectancy ≥12 weeks;
Subjects with chronic HBV infection must have HBV-DNA <500 IU/ml, and have received at least 14 days of anti-HBV treatment (e.g. entecavir, tenofovir) prior to the initiation of study treatment and are willing to receive antiviral treatment throughout the study; Subjects with RNA-positive HCV must have received standard antiviral treatment and the elevation of their liver enzymes must not exceed the level of CTCAE Grade 1;
Adequate vital organ function as shown below:
Blood system function (subjects must have not received blood transfusion or stimulating growth factors within 14 days prior to screening test): neutrophil count ≥1.5×109/L, platelet count ≥ 75×109/L, hemoglobin ≥ 90 g/L; (2) Liver and kidney function (no albumin transfusion within 14 days prior to screening test): serum total bilirubin ≤ 2.5×ULN, serum albumin ≥ 29 g/L, ALT and AST ≤ 5×ULN; serum creatinine <1.5×ULN or eGFR (Cockcroft-Gault formula) ≥ 60 ml/min; (3) Coagulation function: international normalized ratio (INR)≤2.3 or prothrombin time (PT) of ≤ 6 seconds above control; (4) Left ventricular ejection fraction (LVEF) ≥50% by two-dimensional echocardiography.
12. Female subjects (except for females who have underwent surgical sterilization and those have been menopausal for more than one year) who are of childbearing potential are required to adopt a medically proven method for contraception (e.g. intrauterine contraception device, contraceptive pill or condom) throughout the study and up to 120 days after the last dose of investigational products; females who are of childbearing age and who do not underwent surgical sterilization must have negative serum or urine HCG tests within 7 days prior to enrollment; female subjects must not be breastfeeding; male subjects whose partners are of childbearing potential should use effective contraceptive methods throughout the study and up to 120 days after the last dose of investigational product.
13. Subjects who are willing to provide oncological tissues (if applicable) for biomarker test.

Who cannot join

Subjects who have known fibrolamellar carcinoma of liver for phase I and subjects who have fibrolamellar carcinoma, mixed HCC- cholangiocarcinoma or cholangiocarcinoma for phase II;
Subjects with brain metastasis or leptomeningeal metastasis confirmed by brain MRI during screening period;
Subjects with a diagnosis of other malignant tumors within 5 years prior to first administration, except for skin basal cell carcinoma, skin squamous cell carcinoma and/or in situ cancer following radical resection;
Subjects who had liver or other sites loco-regional treatment (including transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), hepatic artery infusion (HAI), local radiotherapy, radioembolization, radiofrequency ablation, cryoablation or percutaneous ethanol injection) , or who had major surgery of liver or other sites within 4 weeks prior to first administration, or had minor surgical procedures (e.g. simple excision, tooth extraction) within one week prior to first administration, or had received palliative radiotherapy for bone metastasis within 2 weeks and radiotherapy-related toxicity ≥ CTCAE Grade 2.
Subjects who have moderate or severe ascites (detected by B-ultrasound or CT), or require therapeutic abdominal paracentesis or drainage;
Subjects with a history of hepatic encephalopathy;

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Subjects with a history of unhealed wounds or ulcers or bone fractures within 3 months prior to study enrollment;
Subjects who plan to have or had allogenic organ or bone marrow transplantation;
Subjects who are at increased risk of bleeding or have history of thrombosis:
Clinically significant bleeding within 3 months prior to screening or clear bleeding tendency; (2) Gastrointestinal hemorrhage within 6 months prior to screening or clear tendency of gastrointestinal hemorrhage; (3) Arterial/venous thromboembolic events within 6 months prior to screening, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, etc.; (4) Require anticoagulation therapy with an agent such as warfarin or heparin; (5) Require chronic anti-platelet therapy (such as aspirin≥100 mg/day, clopidogrel, etc.); 10. Subjects who have clinically significant cardiovascular diseases:
NYHA (New York Heart Association)stage 3 and 4 congestive heart failure;
Unstable angina pectoris or newly diagnosed angina pectoris or myocardial infarction within 12 months prior to screening;
Arrhythmias requiring medications other than β-blockers;
Valvular heart disease of ≥ CTCAE grade 2;
Hypertension inadequately controlled by drugs (systolic pressure >150 mmHg or diastolic pressure >90 mmHg); 11. Subjects who have history of symptomatic pulmonary fibrosis, or have interstitial pneumonitis, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severe impairment of pulmonary function, or other suspicious pulmonary diseases that may interfere with drug-related pulmonary toxicity detection and treatment; 12. Subjects who have suffered active bacterial or fungal infections requiring systemic treatment within 7 days prior to screening; or active tuberculosis; 13. Subjects with active co-infection of Hepatitis B and C, confirmed by positive HBV surface antigen or HBV DNA and HCV RNA 14. Subjects who have any active, known or suspected autoimmune disease; 15. Subjects with a condition requiring systematic treatment with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within 14 days before administration of the investigational drug. In the absence of active autoimmune diseases, inhalation or topical use of steroids (>10 mg/day prednisone or equivalent) is allowed; 16. Other laboratory abnormalities:
Hyponatremia, hypokalemia or hypophosphatemia that have occurred before the first administration, and failed to restore to normal level after electrolyte supplementation therapy; (2) Confirmed diagnosis of thyroid dysfunction, which cannot be maintained within normal range following thyroid hormone replacement therapy; (3) Positive Human immunodeficiency virus (HIV) test; 17. QTc interval >480 ms on two consecutive ECGs; 18. Female subjects during pregnancy or lactation; female subjects of childbearing potential or male subjects who are not willing to use contraception or contraceptive measures during the study; 19. Subjects who have previously received two lines and above tumor immune checkpiont inhibitor treatment, mainly including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, etc, or bispecific antibodies including the above targets, or received anti-LAG-3 antibody; whether subjects who have previously received other tumor immunotherapy can be enrolled should be determined by the sponsor; 20. Known or suspected history of severe allergy to investigational drugs; 21. Subjects who have received live attenuated vaccines or any investigational drugs that have not been marketed in China within 4 weeks prior to first administration; 22. If subjects who have previously used immune checkpoint inhibitors (such as anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies) have the following drug-related adverse events, they will be not suitable for inclusion regardless of recovered or not:
≥ Grade 3 eye-related adverse events
Grade 4 abnormal liver function
≥ Grade 3 neurotoxicity
≥ Grade 3 colitis
≥ Grade 3 renal toxicity
≥ Grade 3 pneumonitis 23. Subjects who are not suitable for inclusion as judged by the investigators.

Trial locations and contacts

1 site in 1 country.

China1 site

Prince of Wales Hospital
Hong Kong, Hong Kong

Other trials in China

About this study

Official title: A Multicenter, Open-label, Phase I/II Dose Escalation and Expansion Clinical Study to Assess the Safety and Efficacy of MGD013 Monotherapy and in Combination With Brivanib Alaninate (ZL-2301) in Patients With Advanced Liver Cancer

This study consists of two parts: Phase I is a dose escalation study to determine the Recommended Phase II Dose (RP2D) of MGD013 monotherapy and that of MGD013 when in combination with Brivanib Alaninate (ZL-2301) in subjects with advanced liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma). Phase II is a dose expansion study and consists of two parts: Part 1 is to assess the safety and efficacy of MGD013 monotherapy and MGD013 in combination with ZL-2301 in subjects with advanced hepatocellular carcinoma (HCC); in Part 2, a therapeutic method (MGD013 monotherapy or MGD013 in combination with ZL-2301, determined by the sponsor according to the obtained data) will be selected for dose expansion study in HCC subjects who have previously failed immune checkpoint inhibitor treatment, to further evaluate the safety and efficacy of the study treatments in the specific group of subjects.

Conditions: Advanced Hepatocellular Carcinoma (HCC)
Being tested: MGD013 monotherapy, MGD013 in combination with Brivanib Alaninate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MGD013 monotherapyDrug
MGD013 monotherapy will start from Phase I dose escalation first, starting dose will be 120mg Q2W, the dose level may escalate sequentially following traditional 3+3 dose escalation scheme (120mg, 240mg, 400mg, 600mg) to determine the RP2D(recommended phase II dose) of MGD013 monotherapy. Then Phase II dose expansion study will initiate, patients will receive the fixed dose of MGD013 monotherapy with RP2D determined in Phase I study.
MGD013 in combination with Brivanib AlaninateDrug
After determining the RP2D of MGD013 monotherapy, MGD013 at the fixed dose will be combined with Brivanib Alaninate. Dose escalation study of the combination therapy in Phase I will adopt traditional 3+3 dose escalation scheme; the dosage of Brivanib will start from 200 mg QD, and may escalate to 400 mg QD, 600 mg QD and a maximum of 800 mg QD to to determine the RP2D of MGD013 in combination with Brivanib Alaninate. Then Phase II dose expansion study will initiate, patients will receive the fixed dose of MGD013 and Brivanib Alaninate combination therapy with RP2D determined in Phase I study.

Study groups in NCT04212221
Study group	Role	What they receive
MGD013	Experimental	MGD013 monotherapy dose escalation and expansion Receives: Drug: MGD013 monotherapy
MGD013+Brivanib Alaninate	Experimental	MGD013+Brivanib Alaninate dose escalation and expansion Receives: Drug: MGD013 in combination with Brivanib Alaninate

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
DLT was defined as the adverse events (AEs) listed in the protocol occurring within 4 weeks (the first 2 cycles, 28 days) after the investigational drugs which were at least possibly related to the study drugs. AE severity was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
Measured: The first two cycles (Cycle 1 and Cycle 2) of the study treatment(s). A cycle lasted for two weeks (14 days) in the study.
Phase 1 and Phase 2: Safety
All adverse events (AEs) occurring on or after the first study treatment were listed and summarized. Treatment-Emergent Adverse Event (TEAE) was defined as an AE that had an onset date or a worsening in severity from baseline on or after the first dose of study treatment (any component of combination treatment whichever is first) up to 30 days following study treatment (any component of combination treatment whichever was last) discontinuation. All adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
Measured: AEs would be collected throughout the clinical trial, from the signing of the informed consent form (ICF) to the end of the trial (until 30 days after the last dose of investigational drugs). Up to approximately 24 months.
Phase 2: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) According to RECIST 1.1
ORR was defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), before progression based on RECIST v1.1. Participants who had no measurable disease at baseline and/or no post-baseline tumor assessment due to any reason will be considered nonresponders. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method.
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.

Secondary outcomes (8)

Phase 2: Objective Response Rate (ORR) by Investigator Assessment According to RECIST 1.1
ORR was defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), before progression based on RECIST v1.1. Participants who had no measurable disease at baseline and/or no post-baseline tumor assessment due to any reason will be considered nonresponders. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method.
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Disease Control Rate (DCR) by BICR / Investigator Assessment According to RECIST 1.1
DCR was defined as the percentage of participants who attained a best overall response status of CR, PR, and SD. If best overall response is SD, the SD should be stable SD, that is the date of SD should be at least 6 weeks after first dose. DCR was analyzed using the same methodology as specified for ORR.
Measured: Radiologic examinations were conducted at basline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Time to Response (TTR) by Investigator Assessment According to RECIST 1.1
TTR was defined as the time from the first dose date to the date of the earliest confirmed response assessed using RECIST V1.1. Only responders were included in the analysis.
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Duration of Response (DoR) by Investigator Assessment According to RECIST 1.1
DoR was defined for subjects with a confirmed objective response as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurred first. Participants who had no progression or death would be censored.
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Progression-Free Survival (PFS) by Investigator Assessment According to RECIST 1.1
PFS was defined as the time from the date of first dose of study treatment (any component of combination treatment whichever is first) to the first documented disease progression as determined by the investigator or BICR with the use of RECIST v1.1, or death from any cause, whichever occurred first. Kaplan-Meier methodology was used to estimate the median PFS for each treatment arm and to construct survival curves for each treatment arm. The Brookmeyer-Crowley methodology was used to construct the 95% CI for the median PFS for each treatment arm (Brookmeyer and Crowley 1982).
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Overall Survival (OS)
OS was defined as the time from the date of the first dose of study treatment (any component of combination treatment whichever was first) to the date of death from any cause. Participants who were alive at the time of the analysis data cutoff would be censored at the last date they were known to be alive. Participants with no post-baseline information were censored at the date of the first dose of study treatment (any study treatment component for combo therapy).
Measured: From the date of the first dose of study treatment to the date of death from any cause. Up to approximately 24 months.
Phase 1: Objective Response Rate (ORR) by Investigator Assessment According to RECIST 1.1
ORR was defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), before progression based on RECIST v1.1. Participants who had no measurable disease at baseline and/or no post-baseline tumor assessment due to any reason will be considered nonresponders. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method.
Measured: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 1: Disease Control Rate (DCR) by Investigator Assessment According to RECIST 1.1
DCR was defined as the percentage of participants who attained a best overall response status of CR, PR, and SD. If best overall response is SD, the SD should be stable SD, that is the date of SD should be at least 6 weeks after first dose. DCR was analyzed using the same methodology as specified for ORR.
Measured: Radiologic examinations were conducted at basline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Apr 202027 Apr 2022

First posted26 Dec 2019
Study start20 Apr 2020
Primary completion27 Apr 2022
Study completion27 Apr 2022

Why it stopped: Due to the rapid shifting of liver cancer disease landscape and the company's adjustment of development strategy.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Advanced Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 89 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04212221
Sponsor's protocol ID: ZL-MGD013-202
Status last verified: Jun 2024
First submitted: 19 Dec 2019
Last updated: 23 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Open-label, Phase I/II Dose Escalation and Expansion Clinical Study to Assess the Safety and Efficacy of MGD013 Monotherapy and in Combination With Brivanib Alaninate (ZL-2301) in Patients With Advanced Liver Cancer
ClinicalTrials.gov ID: NCT04212221
Acronym / sponsor ID: ZL-MGD013-202
Conditions: Advanced Hepatocellular Carcinoma (HCC)
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to the rapid shifting of liver cancer disease landscape and the company's adjustment of development strategy.
Enrolment: 89 participants (actual)
Lead sponsor: Zai Lab (Shanghai) Co., Ltd.Industry (pharma, biotech, devices)
Study start: 20 Apr 2020 (actual)
Primary completion: 27 Apr 2022 (actual)
Study completion: 27 Apr 2022 (actual)
First posted: 26 Dec 2019 (actual)
Results: Posted 23 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
MGD013	Experimental	Drug: MGD013 monotherapyMGD013 monotherapy dose escalation and expansion
MGD013+Brivanib Alaninate	Experimental	Drug: MGD013 in combination with Brivanib AlaninateMGD013+Brivanib Alaninate dose escalation and expansion

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Subjects who voluntarily sign the informed consent form (ICF);
Male or female subjects who are aged 18-75 years old;
Subjects with histologic, cytologic or clinical confirmed diagnosis of advanced HCC (Phase I could include intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma), and are not suitable for surgery or loco-regional therapy or have progressed following surgery and/or loco-regional therapy;
Subject who has at least one measurable lesion according to RECIST v1.1 criteria.
Phase I study: subjects who have previously received at least one line of systemic therapy, including immune checkpoint inhibitors, molecular targeted drugs or systematic chemotherapy, alone or in combination, and failed (progression confirmed by imaging) or were intolerant at the discretion of investigator; PhaseII：Advanced HCC cohort with subjects who have previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) prior one line immune checkpoint inhibitor treatment, including anti-PD-1 antibody/anti-PD-L1 antibody and / or anti-CTLA-4 antibody, and/or molecular targeted therapy or systematic chemotherapy (monotherapy or in combination); Phase II: Advanced HCC cohort with subjects who have not previously received immune checkpoint inhibitor treatment: subjects who have failed (progression confirmed by imaging) or were intolerant to (at the discretion of investigator) previous molecular targeted therapy or systematic chemotherapy, without receiving immune checkpoint inhibitor treatment (including anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, and bispecific antibodies including the above targets).

Key exclusion criteria (22 listed)

Subjects who have known fibrolamellar carcinoma of liver for phase I and subjects who have fibrolamellar carcinoma, mixed HCC- cholangiocarcinoma or cholangiocarcinoma for phase II;
Subjects with brain metastasis or leptomeningeal metastasis confirmed by brain MRI during screening period;
Subjects with a diagnosis of other malignant tumors within 5 years prior to first administration, except for skin basal cell carcinoma, skin squamous cell carcinoma and/or in situ cancer following radical resection;
Subjects who had liver or other sites loco-regional treatment (including transcatheter arterial chemoembolization (TACE), transcatheter arterial embolization (TAE), hepatic artery infusion (HAI), local radiotherapy, radioembolization, radiofrequency ablation, cryoablation or percutaneous ethanol injection) , or who had major surgery of liver or other sites within 4 weeks prior to first administration, or had minor surgical procedures (e.g. simple excision, tooth extraction) within one week prior to first administration, or had received palliative radiotherapy for bone metastasis within 2 weeks and radiotherapy-related toxicity ≥ CTCAE Grade 2.
Subjects who have moderate or severe ascites (detected by B-ultrasound or CT), or require therapeutic abdominal paracentesis or drainage;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MGD013 monotherapyMGD013 monotherapy will start from Phase I dose escalation first, starting dose will be 120mg Q2W, the dose level may escalate sequentially following traditional 3+3 dose escalation scheme (120mg, 240mg, 400mg, 600mg) to determine the RP2D(recommended phase II dose) of MGD013 monotherapy. Then Phase II dose expansion study will initiate, patients will receive the fixed dose of MGD013 monotherapy with RP2D determined in Phase I study.	Drug	MGD013
MGD013 in combination with Brivanib AlaninateAfter determining the RP2D of MGD013 monotherapy, MGD013 at the fixed dose will be combined with Brivanib Alaninate. Dose escalation study of the combination therapy in Phase I will adopt traditional 3+3 dose escalation scheme; the dosage of Brivanib will start from 200 mg QD, and may escalate to 400 mg QD, 600 mg QD and a maximum of 800 mg QD to to determine the RP2D of MGD013 in combination with Brivanib Alaninate. Then Phase II dose expansion study will initiate, patients will receive the fixed dose of MGD013 and Brivanib Alaninate combination therapy with RP2D determined in Phase I study.	Drug	MGD013+Brivanib Alaninate

Primary outcome

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: The first two cycles (Cycle 1 and Cycle 2) of the study treatment(s). A cycle lasted for two weeks (14 days) in the study.
DLT was defined as the adverse events (AEs) listed in the protocol occurring within 4 weeks (the first 2 cycles, 28 days) after the investigational drugs which were at least possibly related to the study drugs. AE severity was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
Phase 1 and Phase 2: Safety
Time frame: AEs would be collected throughout the clinical trial, from the signing of the informed consent form (ICF) to the end of the trial (until 30 days after the last dose of investigational drugs). Up to approximately 24 months.
All adverse events (AEs) occurring on or after the first study treatment were listed and summarized. Treatment-Emergent Adverse Event (TEAE) was defined as an AE that had an onset date or a worsening in severity from baseline on or after the first dose of study treatment (any component of combination treatment whichever is first) up to 30 days following study treatment (any component of combination treatment whichever was last) discontinuation. All adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
Phase 2: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
ORR was defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), before progression based on RECIST v1.1. Participants who had no measurable disease at baseline and/or no post-baseline tumor assessment due to any reason will be considered nonresponders. An estimate of ORR was calculated for each treatment arm, and its 95% CI was calculated using the Clopper-Pearson method.

8 secondary outcomes

Phase 2: Objective Response Rate (ORR) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Disease Control Rate (DCR) by BICR / Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at basline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Time to Response (TTR) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Duration of Response (DoR) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Progression-Free Survival (PFS) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 2: Overall Survival (OS)
Time frame: From the date of the first dose of study treatment to the date of death from any cause. Up to approximately 24 months.
Phase 1: Objective Response Rate (ORR) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.
Phase 1: Disease Control Rate (DCR) by Investigator Assessment According to RECIST 1.1
Time frame: Radiologic examinations were conducted at basline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.

Results and safety

Results posted to the registry on 23 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1: MGD013 120mg	1	0
Phase 1: MGD013 240mg	3	0
Phase 1: MGD013 400mg	3	0
Phase 1: MGD013 600mg	6	0
Phase 1: MGD013 400mg + Brivanib 400mg	3	0
Phase 1: MGD013 600mg + Brivanib 400mg	4	0
Phase 2: MGD013 600mg Post-CPI Cohort	33	0
Phase 2: MGD013 600mg CPI-naive Cohort	36	0

Primary outcome: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

Time frame: The first two cycles (Cycle 1 and Cycle 2) of the study treatment(s). A cycle lasted for two weeks (14 days) in the study.. Count of participants. Unit: Participants

Measure	Phase 1: MGD013 120mg n = 1	Phase 1: MGD013 240mg n = 3	Phase 1: MGD013 400mg n = 3	Phase 1: MGD013 600mg n = 6	Phase 1: MGD013 400mg + Brivanib 400mg n = 3	Phase 1: MGD013 600mg + Brivanib 400mg n = 4
Value	0	0	0	0	0	0

Population analysed: All patients who received at least one dose of study treatment (any component of combination treatment whichever is first).

Primary outcome: Phase 1 and Phase 2: Safety

Time frame: AEs would be collected throughout the clinical trial, from the signing of the informed consent form (ICF) to the end of the trial (until 30 days after the last dose of investigational drugs). Up to approximately 24 months.. Count of participants. Unit: Participants

Measure	Phase 1: MGD013 120mg n = 1	Phase 1: MGD013 240mg n = 3	Phase 1: MGD013 400mg n = 3	Phase 1: MGD013 600mg n = 6	Phase 1: MGD013 400mg + Brivanib 400mg n = 3	Phase 1: MGD013 600mg + Brivanib 400mg n = 4	Phase 2: MGD013 600mg Post-CPI Cohort n = 33	Phase 2: MGD013 600mg CPI-naive Cohort n = 36
Patients with at Least One TEAE	1	3	3	6	3	4	31	34
TEAEs with Grade 3 or Higher	1	1	0	2	1	2	11	10
Serious TEAEs	0	1	0	1	0	1	10	8
TEAEs Leading to Death	0	0	0	0	0	0	0	1
TEAEs Leading to Treatment Discontinuation of Any Treatment Component	0	0	0	0	0	0	2	3
TEAEs Leading to Dose Modification of Any Treatment Component	1	2	0	1	2	3	13	15
Treatment-Related TEAEs	1	2	3	6	3	4	23	27
Treatment-Related TEAEs with Grade 3 or Higher	1	1	0	1	1	1	5	8

Population analysed: All patients who received at least one dose of study treatment (any component of combination treatment whichever is first).

Primary outcome: Phase 2: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) According to RECIST 1.1

Time frame: Radiologic examinations were conducted at baseline within 28 days prior to the start of study medication and every 8 weeks (±7 days) dated from the first day of the first cycle until disease progression. Up to approximately 24 months.. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Phase 2: MGD013 600mg Post-CPI Cohort n = 33	Phase 2: MGD013 600mg CPI-naive Cohort n = 36
Value	3.0 (0.08 to 15.76)	8.3 (1.75 to 22.47)

Population analysed: All patients who received at least one dose of study treatment (any component of combination treatment whichever is first) in phase 2.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the date of administration of the first dose of study treatment (any component of combination treatment whichever is first) up to 30 days following study treatment discontinuation (any component of combination treatment whichever is last). Adverse event reporting for all-cause mortality considers all deaths that occurred during the study. Up to approximately 24 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1: MGD013 120mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Phase 1: MGD013 240mg	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Phase 1: MGD013 400mg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Phase 1: MGD013 600mg	1 of 6 (16.7%)	6 of 6 (100%)	1 of 6
Phase 1: MGD013 400mg + Brivanib 400mg	0 of 3 (0%)	3 of 3 (100%)	2 of 3
Phase 1: MGD013 600mg + Brivanib 400mg	1 of 4 (25%)	4 of 4 (100%)	1 of 4
Phase 2: MGD013 600mg Post-CPI Cohort	10 of 33 (30.3%)	30 of 33 (90.9%)	10 of 33
Phase 2: MGD013 600mg CPI-naive Cohort	8 of 36 (22.2%)	34 of 36 (94.4%)	11 of 36

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

ZhengGang Ren, PhD principal investigator

Fudan University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: The first two cycles (Cycle 1 and Cycle 2) of the study treatment(s). A cycle lasted for two weeks (14 days) in the study.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04212221.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2024; AzTrials last refreshed its copy on 6 Nov 2026.