A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib Plus Tislelizumab or Combination With Nab-paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC)

NCT04734262 | Unknown Phase 2

• 1 other identifier: BGB-900-2001-IIT
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the efficacy and safety of sitravatinib plus tislelizumab or combination with nab-paclitaxel in locally recurrent or metastatic triple-negative breast cancer (TNBC) patients.

Conditions

Metastatic Breast Cancer

Keywords

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) by Investigator in Cohort A, Cohort B and Cohort C

  The number of people with tumor responses according to RECIST (V1.1): the proportion of participants who achieves a best overall response of complete response (CR) or partial response (PR).

  Up to 12 months

• Number of participants experiencing ≥ Grade 3 TRAEs in Cohort B

  TRAE are adverse events that occur during or after the first administration of the study drug until 30 days after the study drug is discontinued or the new anticancer treatment is initiated.

  Up to 12 months

Secondary Outcomes (7)

• Duration of Response (DOR) by Investigator in Cohort A, Cohort B and Cohort C

  Up to 12 months

• Disease Control Rate (DCR) by Investigator in Cohort A, Cohort B and Cohort C

  Up to 12 months

• Progression-free Survival (PFS) by Investigator in Cohort A, Cohort B and Cohort C

  Up to 12 months

• One-year overall survival (OS) rate in Cohort A, Cohort B and Cohort C

  Up to 12 months

• Number of participants experiencing Adverse Events (AEs), Treatment-Related Adverse Events (TRAEs) or Serious Adverse Events (SAEs) in Cohort A, Cohort B and Cohort C

  Up to 12 months

Study Arms (3)

Cohort A

EXPERIMENTAL

Subjects will receive 70mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Sitravatinib; Drug: Tislelizumab

Cohort B

EXPERIMENTAL

Subjects will receive 100mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Sitravatinib; Drug: Tislelizumab

Cohort C

EXPERIMENTAL

Subjects will receive sitravatinib in combination with 200mg tislelizumab and 100 mg/m2 nab-paclitaxel until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Sitravatinib; Drug: Tislelizumab; Drug: Nab-paclitaxel

Interventions

Sitravatinib DRUG

Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases

Also known as: MGCD516

Cohort A; Cohort B; Cohort C

Tislelizumab DRUG

Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody

Also known as: BGB-A317

Cohort A; Cohort B; Cohort C

Nab-paclitaxel DRUG

Nab-paclitaxel D1, D8 Q3W IV Nab-paclitaxel is a chemotherapy drug which combines the chemotherapy drug paclitaxel with albumin

Also known as: Nanoparticle albumin-bound paclitaxel

Cohort C

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
• Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
• Histologically confirmed diagnosis of TNBC characterized by estrogen-receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2 receptor negative (HER2-);
• ≤ 3 prior lines of systemic therapy
• For patients refractory/resistant to anti-PD-1/PD-L1 antibodies, there should be no anti-PD-1/PD-L1 treatment-related toxicity from prior therapies
• Previously untreated for metastatic setting or recurred/metastasized after surgery for locally recurrent or metastatic breast cancer (cohort C), and the time from previous neo-/adjuvant therapy to recurrence met the following requirements: ≥ 6 months interval between the end of neo-/adjuvant paclitaxel-based treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant anti-angiogenic treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant immunotherapy and recurrence/metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
• Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)

You may not qualify if:

• Active leptomeningeal disease or uncontrolled brain metastasis
• Active autoimmune diseases or history of autoimmune diseases that may relapse
• Any active malignancy ≤ 2 years
• Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s)
• History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
• Known history of human immunodeficiency virus (HIV) infection
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers
• Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
• Prior allogeneic stem cell transplantation or organ transplantation
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
• Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
• Inability to swallow capsules or disease significantly affecting gastrointestinal function

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (2)

• Lei Fan, Xiyu Liu, Xi Jin, Yunsong Yang, Li Chen, Xin Hu, Zhonghua Wang, Yizhou Jiang, and Zhimin Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer.Journal of Clinical Oncology 2022 40:16_suppl, 1070-1070

  RESULT

• L. Liu, X. Jin, Y. Xu, S. Wu, Y. Yang, L. Chen, W. Zhang, L. Ma, X. Hu, Z. Wang, Y. Jiang, Z. Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients (pts) with locally recurrent or metastatic triple negative breast cancer (TNBC): a multi-cohort, phase II trial. Annals of Oncology (2022) 16 (suppl_1): 100102-100102. 10.1016/iotech/iotech100102

  RESULT

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

sitravatinib; tislelizumab; 130-nm albumin-bound paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Officials

• Zhimin Shao, MD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Model Details: Cohort A Subjects will receive 70mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Cohort B Subjects will receive 100mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Cohort C Subjects will receive sitravatinib in combination with 200mg tislelizumab and 100 mg/m2 nab-paclitaxel until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 2, 2021
• Study Start: April 1, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

CN (1)