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Gastric CancerPhase 1NCT04178460

A Study of Niraparib Combined With MGD013 in Patients With Advanced or Metastatic Solid Tumor Who Failed Prior Treatment

A Phase 1 study testing Niraparib combined with MGD013 in people with Gastric Cancer and Triple Negative Breast Cancer, run by Zai Lab (Shanghai) Co., Ltd. at 19 sites 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

This is a a Multicenter, Open-label, Single-arm, Phase Ib Dose Escalation and Multi-cohort Expansion Clinical Study to Assess the Safety and Antitumor Activity of Niraparib in Combination with MGD013 in Patients with Advanced or Metastatic Solid Tumor Who Failed Prior Treatment. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Niraparib combined with MGD013
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
19 sitesChina
Study dates
3 Feb 2020to 2 Mar 2022
Phase
Phase 1
Are there results?
None posted in the registry

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 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent form.
  • ≥ 18 years old.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  • Subjects who have at least one measurable lesion according to RECIST v1.1 criterion (only applicable for subjects at dose expansion part).
  • Subjects with adequate organ function.
  • Subjects with life expectancy of 12 weeks or more.
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  • Dose escalation part and EXP-1 gastric cancer (including gastroesophageal junction cancer)
  • Subjects with histologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma;
  • Subjects who have previously failed at least 2 prior systemic treatment for locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma; treatment failure is defined as the occurrence of disease progression or intolerable adverse events during treatment. Subjects who have progressed on first-line chemotherapy with platinum and fluoropyrimidine for advanced disease, and who are deemed unfit/ineligible for further chemotherapy or anti-angiogenesis therapy may also be eligible;
  • EXP-2 triple negative breast cancer (TNBC)
  • Subjects with metastatic or inoperable locally advanced, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression based on most recently analyzed biopsy or archived tissue;
  • Subjects with disease progression or relapse after ≥ 2 prior lines of standard chemotherapy regimens in the locally advanced or metastatic disease stage (if the disease is progressed to unresectable locally advanced or metastatic disease within 12 months after adjuvant or neoadjuvant chemotherapy for limited-stage disease, it can be counted as 1 prior line);
  • Subjects with LAG-3 expression meeting the criteria of moderate or high expression (confirmed by the central laboratory);
  • Subjects who have undergone prior taxane therapy regardless of disease stage (adjuvant, neoadjuvant, or advanced) at the time of treatment; or subjects who are not eligible for taxane therapy because of contraindications;
  • EXP-3 biliary tract carcinoma
  • Subjects with histologically confirmed, surgically unresectable locally advanced, recurrent or metastatic biliary track carcinoma (BTC), including cholangiocarcinoma or gallbladder carcinoma;
  • Subjects with disease progression or relapse after ≥ 1 prior standard chemotherapy regimen. If the patient received preoperative neoadjuvant chemotherapy or adjuvant chemotherapy after R0 radical resection, and the disease progression occurred during the chemotherapy or within 6 months after discontinuation of chemotherapy, it may be counted as first-line treatment failure;
  • Subjects with LAG3 expression meeting the criteria for moderate or high expression (confirmed by the central laboratory);
  • Subjects without known IDH-1 mutations or FGFR2 fusions (if status is unknown, the subject will be included without the need for active testing).
  • EXP-4 endometrial carcinoma
  • Subjects with histologically confirmed advanced or metastatic endometrial carcinoma;
  • Subjects with disease progression or relapse after ≥ 1 prior standard chemotherapy regimen in the advanced or metastatic stage;
  • Subjects with LAG-3 expression meeting the criteria for moderate or high expression (confirmed by the central laboratory);
  • Subjects without carcinosarcomas, endometrial leiomyosarcomas, or other high-grade sarcomas, or endometrial stromal sarcomas.

Who cannot join

  • Known hypersensitivity to niraparib or active or inactive ingredients of drugs with similar chemical structure to niraparib.
  • Subjects who have previously received PARP inhibitors (including niraparib) treatment; anti-LAG-3 treatment.
  • Subjects who have received treatment with other investigational drugs within 4 weeks prior to the first dose of study drug or < 5 elimination half-lives of the investigational drug (whichever is longer); subjects who have underwent a major surgery within 4 weeks prior to the start of study, or with any surgical side effects that have not been recovered.
  • Subjects who experienced ≥ Grade 3 anemia, neutropenia or thrombocytopenia due to prior chemotherapy, which lasted more than 4 weeks.
  • Subjects who experienced transfusion dependent anemia or thrombocytopenia, including:
  • Blood (platelet or red blood cell) transfusion within 2 weeks prior to the first dose;
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  • Subjects who previously received colony stimulating factor treatment (e.g., granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF) or recombinant erythropoietin) within 2 weeks prior to the first dose.
  • Untreated or symptomatic brain metastases or leptomeningeal metastases (e.g., new or worsening symptoms or vital signs, or unstable dose of hormones required). Note: There is no need for the imaging scan to confirm absence of brain metastases; subjects with spinal cord compression who have previously received definitive therapy and have an evidence for clinically stable disease at least > 28 days can be enrolled.
  • Subjects who have received palliative radiotherapy on > 20% bone marrow area within 3 weeks prior to enrollment.
  • Subjects who have other invasive cancers (except treated in situ cancer, non-melanoma skin cancer, localized prostate cancer (Gleason score < 6), etc.) other than gastric cancer, endometrial carcinoma, biliary tract carcinoma and breast cancer within 5 years prior to enrollment.
  • Subjects who have been previously or are currently diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  • Subjects who have severe or uncontrolled diseases, including but not limited to:
  • Digestive tract hemorrhage within 2 months prior to enrollment or currently active digestive tract hemorrhage;
  • Uncontrolled nausea and vomiting, inability to swallow the investigational drugs, or any gastrointestinal diseases that may intervene with and influence drug absorption and metabolism;
  • Human immunodeficiency virus (HIV) infection, active hepatitis (e.g., hepatitis B (HBV-DNA > 500 IU/ml), hepatitis C virus ribonucleic acid (HCV-RNA) positive);
  • Uncontrolled ventricular arrhythmia, myocardial infarction that occurred within 3 months prior to enrollment;
  • Uncontrolled grand mal seizure, unstable spinal cord compression, superior vena cava syndrome or other mental disorders influencing subjects to sign informed consent forms;
  • Immunodeficiency (except splenectomy).
  • Subjects with known or suspected history of autoimmune disease, except: vitiligo and psoriasis that does not require systemic treatment (in recent two years); subjects with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
  • Treatment with systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) or other immunosuppressive drugs within 14 days prior to the initiation of the study treatment.
  • If patients who have previously used immune checkpoint inhibitors (such as anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies) have the following adverse events related to immune checkpoint inhibitors, they will be not suitable for inclusion regardless of recovered or not:
  • ≥ Grade 3 eye-related adverse events;
  • Abnormal hepatic function met Hy's Law criteria;
  • ≥ Grade 3 neurotoxicity;
  • ≥ Grade 3 colitis;
  • ≥ Grade 3 renal toxicity.
  • Subjects with a history of pneumonitis requiring steroid treatment or current pneumonitis.
  • Subjects with previous or current disease, treatment, or laboratory abnormality that may intervene with study results and affect subjects participating in the study, or subjects not suitable for participation in the study at the investigator's discretion.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

China19 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality

  • Beijing Cancer Hospital

    Beijing

  • Sichuan Cancer Hospital

    Chengdu, Sichuan

  • Sun Yat-Sen University Cancer Center

    Guangzhou, Guangdong

  • Sun Yat-Sen University Cancer Center

    Guangzhou

  • The Affiliated Tumor Hospital of Harbin Medical University

    Ha’erbin

  • The First Affiliated Hospital Zhejiang University School Of Medicine

    Hangzhou, Zhejiang

  • The Chinese University of Hong Kong, Prince of Wales Hospital

    Hong Kong

  • The University of Hong Kong, Queen Mary Hospital

    Hong Kong

  • Obstetrics & Gynecology Hospital of Fudan University

    Shanghai, Shanghai Municipality

  • Liaoning Cancer hospital

    Shenyang, Liaoning

  • Taizhou Hospital of Zhejiang Province

    Taizhou

  • TianJin Medical University General Hospital

    Tianjin, Tianjin Municipality

  • Hubei Cancer Hospital

    Wuhan, Hubei

  • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

    Wuhan

  • First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, Shaanxi

  • Sir Run Shaw Hospital, School Of Medicine ,Zhejiang University

    Zhejiang

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

  • Henan Cancer Hospital

    Zhengzhou, Henan

Other trials in China

About this study

Official title: A Multicenter, Open-label, Single-arm, Phase Ib Dose Escalation and Multi-cohort Expansion Clinical Study to Assess the Safety and Antitumor Activity of Niraparib in Combination With MGD013 in Patients With Advanced or Metastatic Solid Tumor Who Failed Prior Treatment

This is a a Multicenter, Open-label, Single-arm, Phase Ib Dose Escalation and Multi-cohort Expansion Clinical Study to Assess the Safety and Antitumor Activity of Niraparib in Combination with MGD013 in Patients with Advanced or Metastatic Solid Tumor Who Failed Prior Treatment.

This study consists of dose escalation part and dose expansion part.'3+3'design will be adopted in the dose escalation part in subjects with advanced or metastatic gastric cancer who failed prior treatment. The dose of niraparib will be fixed and determined based on baseline weight and platelet count of subjects. Dose expansion part will be expanded at the specified dose level to further assess the safety and preliminary antitumor activity.

Being tested
Niraparib combined with MGD013
Medical subject headings
Stomach Neoplasms, Triple Negative Breast Neoplasms, Endometrial Neoplasms

What participants receive

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

  • Niraparib combined with MGD013Drug

    The dose escalation part will enroll about 9 - 24 Gastric cancer (including gastroesophageal junction cancer) subjects, with fixed dose niraparib (200mg or 300mg) combined with MGD013 (120mg, 300mg or 600mg ) in different dose level.

    For the dose expansion part, patients with advanced or metastatic Gastric cancer (including gastroesophageal junction cancer), Triple negative breast cancer, Biliary tract carcinoma, Endometrial carcinoma will be enrolled, about 35 subjects for each expansion cohort during dose expansion phase with fixed dose niraparib (200mg or 300mg) combined with fixe dose MGD013 (to be confirmed after dose escalation).

Study groups in NCT04178460
Study groupRoleWhat they receive
Assigned InterventionsExperimentalNiraparib combined with MGD013
Receives: Drug: Niraparib combined with MGD013

What is being measured

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

  1. Safety and Validity profiles

    Phase I Dose Escalation Part:

    • To determine the dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of niraparib in combination with MGD013 in patients with advanced or metastatic gastric cancer;
    • To determine the recommended phase II dose (RP2D) of niraparib in combination with MGD013 in patients with advanced or metastatic solid tumors.

    Measured: approximately 45months

  2. Validity profiles

    Phase I Dose Expansion Part:

    • To assess the objective response rate (ORR) of niraparib in combination with MGD013 in patients with different types of advanced or metastatic solid tumors.

    Measured: approximately 45months

Secondary outcomes (3)

  1. Safety and Validity profiles

    Phase I Dose Escalation Part:

    • To assess the safety and tolerability of different doses levels of niraparib in combination with MGD013 in patients with advanced or metastatic gastric cancer;
    • To assess the preliminary antitumor activity of niraparib in combination with MGD013 in patients with advanced or metastatic gastric cancer, including objective response rate (ORR), disease control rate (DCR), etc.

    Measured: approximately 45months

  2. Safety and Validity profiles

    Phase I Dose Expansion Part:

    • To assess other antitumor activity of niraparib in combination with MGD013 in patients with different types of advanced or metastatic solid tumors, including duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS);
    • To assess the safety and tolerability of niraparib in combination with MGD013 in patients with different types of advanced or metastatic solid tumors.
    • To assess the antitumor activity of niraparib in combination with MGD013 in patients with different HRR gene status, expression level of PD-L1 and LAG-3.

    Measured: approximately 45months

  3. Exploratory objective

    To explore the correlation between other biomarkers related to MGD013/niraparib and subject safety, antitumor activity.

    Measured: approximately 45months

Timeline

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

  1. First posted26 Nov 2019
  2. Study start3 Feb 2020
  3. Primary completion2 Mar 2022
  4. Study completion2 Mar 2022

Why it stopped: This termination decision is a business decision and is not due to any safety concerns.

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04178460
Sponsor's protocol ID
ZL-2306-006
Status last verified
May 2022
First submitted
25 Nov 2019
Last updated
1 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Qiu MZ, Pan H, Lam KO, Wang J, Zheng Y, Li H, Wu X, Wang L, Bao L, Cheng J, Shi Y, Gao Y, Yan M, Luo H, Zheng Y, Zhen X, Hang W, Hou J, Xu RH. Tebotelimab plus niraparib in previously treated locally advanced or metastatic solid tumors: A phase 1b dose escalation and expansion study. Cancer. 2025 Jun 1;131(11):e35919. doi: 10.1002/cncr.35919.

    PubMed 40445839

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Niraparib combined with MGD013 in people with Gastric Cancer and Triple Negative Breast Cancer, run by Zai Lab (Shanghai) Co., Ltd. at 19 sites in China.

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 24 inclusion and 28 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 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites 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 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.

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

Are results available for this study?

The study was stopped early (reason given: This termination decision is a business decision and is not due to any safety concerns.). Results are not available in the source record.

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?

Safety and Validity profiles (time frame: approximately 45months). The study lists 2 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 NCT04178460, which also lists 1 linked publication.

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 1 Jun 2022; AzTrials last refreshed its copy on 6 Nov 2026.

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