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

NCT04178460 | Terminated Phase 1 DMC

• 1 other identifier: ZL-2306-006
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 19

Brief 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. 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.

Conditions

Gastric Cancer; Triple Negative Breast Cancer; Biliary Tract Carcinoma; Endometrial Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  approximately 45months

• 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.

  approximately 45months

Secondary Outcomes (3)

• Safety and Validity profiles

  approximately 45months

• Safety and Validity profiles

  approximately 45months

• Exploratory objective

  approximately 45months

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

Niraparib combined with MGD013

Drug: Niraparib combined with MGD013

Interventions

Niraparib combined with MGD013 DRUG

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).

Assigned Interventions

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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;
• 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);

Sponsors & Collaborators

• Zai Lab (Shanghai) Co., Ltd.: lead

Study Sites (19)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, China

Location

Liaoning Cancer hospital

Shenyang, Liaoning, China

Location

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Location

Obstetrics & Gynecology Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Sichuan Cancer Hospital

Chengdu, Sichuan, China

Location

TianJin Medical University General Hospital

Tianjin, Tianjin Municipality, China

Location

The First Affiliated Hospital Zhejiang University School Of Medicine

Hangzhou, Zhejiang, China

Location

Beijing Cancer Hospital

Beijing, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, China

Location

The Affiliated Tumor Hospital of Harbin Medical University

Ha’erbin, China

Location

The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong, China

Location

The University of Hong Kong, Queen Mary Hospital

Hong Kong, China

Location

Taizhou Hospital of Zhejiang Province

Taizhou, China

Location

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

Wuhan, China

Location

Sir Run Shaw Hospital, School Of Medicine ,Zhejiang University

Zhejiang, China

Location

Related Publications (1)

• 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.

  PMID: 40445839 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Triple Negative Breast Neoplasms; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 26, 2019
• Study Start: February 3, 2020
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Locations

CN (19)