A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib and Tislelizumab in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT04734262
• Recruitment Status: Not yet recruiting
• First Posted: February 2, 2021
• Last Update Posted: February 2, 2021
• Sponsor: Fudan University
• Information provided by (Responsible Party): Zhimin Shao, Fudan University

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy and safety of tislelizumab in combination with sitavatinib in advanced triple-negative breast cancer patients.

Condition or disease	Intervention/treatment	Phase
Metastatic Breast Cancer	Drug: Sitravatinib; Drug: Tislelizumab	Phase 2

Detailed Description:

This is a prospective, single-arm, single-center, two cohorts, Simon's two-stage design, phase II clinical trial in advanced triple-negative breast cancer patients. Subjects will be divided into two cohorts by different treatment dose of sitravatinib. Cohort A patients will receive 70mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV); Cohort B patients will receive 100mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV). Subjects in both cohorts will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, and investigators determine that medication must be discontinued. Drug efficacy and safety data will be collected.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 61 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment

Intervention Model Description

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.

• Masking: None (Open Label)
• Masking Description: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib and Tislelizumab in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC)
• Estimated Study Start Date: January 30, 2021
• Estimated Primary Completion Date: October 30, 2022
• Estimated Study Completion Date: January 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Sitravatinib; Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases; Other Name: MGCD516; Drug: Tislelizumab; Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Name: BGB-A317
Experimental: 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.	Drug: Sitravatinib; Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases; Other Name: MGCD516; Drug: Tislelizumab; Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody; Other Name: BGB-A317

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) by Investigator in Cohort A and Cohort B [ Time Frame: Up to 12 months ]
   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).
2. Number of participants experiencing ≥ Grade 3 TRAEs in Cohort B [ Time Frame: Up to 12 months ]
   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.

Secondary Outcome Measures :

1. Duration of Response (DOR) by Investigator in Cohort A and Cohort B [ Time Frame: Up to 12 months ]
   The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
2. Disease Control Rate (DCR) by Investigator in Cohort A and Cohort B [ Time Frame: Up to 12 months ]
   The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).
3. Progression-free Survival (PFS) by Investigator in Cohort A and Cohort B [ Time Frame: Up to 12 months ]
   Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.
4. One-year overall survival (OS) rate n Cohort A and Cohort B [ Time Frame: Up to 12 months ]
   OS defined as the time from the date of randomization to the date of death due to any reason. One-year survival rate (percentage of subjects alive at 1 year) was estimated from OS data.
5. Number of participants experiencing Adverse Events (AEs) or Serious Adverse Events (SAEs) in Cohort A [ Time Frame: Up to 12 months ]
6. Number of participants experiencing AEs or SAEs in Cohort B other than Grade 3 TRAEs [ Time Frame: Up to 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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
• 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)

Exclusion Criteria:

• 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
• Pregnant or breastfeeding woman NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Zhimin Shao, MD, PhD; 86-021-64175590 ext 88807; zhimingshao@yahoo.com

Contact: Lei Fan, MD; 86-021-64175590 ext 88603; teddyfl@163.com

Sponsors and Collaborators

Fudan University

Investigators

• Principal Investigator: Zhimin Shao, MD, PhD; Fudan University

More Information

• Responsible Party: Zhimin Shao, Chief Physician, Fudan University
• ClinicalTrials.gov Identifier: NCT04734262
• Other Study ID Numbers: BGB-900-2001-IIT
• First Posted: February 2, 2021
• Last Update Posted: February 2, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhimin Shao, Fudan University:

Triple Negative Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms; Triple Negative Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases