Pelareorep and Paclitaxel Injection in Chinese Patients With Advanced or Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT05519059
• Recruitment Status: Completed
• First Posted: August 29, 2022
• Last Update Posted: November 22, 2023
• Sponsor: Adlai Nortye Biopharma Co., Ltd.
• Information provided by (Responsible Party): Adlai Nortye Biopharma Co., Ltd.

Tracking Information

• First Submitted Date: August 25, 2022
• First Posted Date: August 29, 2022
• Last Update Posted Date: November 22, 2023
• Actual Study Start Date: October 11, 2021
• Actual Primary Completion Date: September 29, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 25, 2022)

Number of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 4 Weeks ]

DLTs are defined as study drug-related toxicities graded using Common Terminology Criteria for Adverse events of the National Cancer Institute (NCI CTCAE) V5.0 occurring during DLT period (the first 4 weeks of AN0025 administration in combination with dCRT)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 28, 2022)

• Objective response rate (ORR) [ Time Frame: 24 months ]
  The rate of patients with complete response and partial response in all tumor evaluable patients
• Disease control rate (DCR) [ Time Frame: 24 months ]
  The rate of patients with complete response, partial response and stable disease in all tumor evaluable patients
• Progression-free survival (PFS) [ Time Frame: 24 months ]
  The duration from the date of 1st dose to imaging progression or death, which earlier
• Duration of response (DOR) [ Time Frame: 24 months ]
  The duration from the first PR/CR to progression
• Overall survival (OS) [ Time Frame: 24 months ]
  The duration from the date of 1st dose to death

Original Secondary Outcome Measures (submitted: August 25, 2022)

• Objective response rate (ORR) [ Time Frame: 24 months ]
  The rate of patients with complete response and partial response in all tumor evaluable patients 2) To preliminarily evaluate the efficacy of Pelareorep combined with Paclitaxel Injection for the treatment of Chinese patients with advanced or metastatic breast cancer.
• Disease control rate (DCR) [ Time Frame: 24 months ]
  The rate of patients with complete response, partial response and stable disease in all tumor evaluable patients
• Progression-free survival (PFS) [ Time Frame: 24 months ]
  The duration from the date of 1st dose to imageological progression or death, which earlier
• Duration of response (DOR) [ Time Frame: 24 months ]
  The duration from the first PR/CR to progression
• Overall survival (OS) [ Time Frame: 24 months ]
  The duration from the date of 1st dose to death

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pelareorep and Paclitaxel Injection in Chinese Patients With Advanced or Metastatic Breast Cancer
• Official Title: A Multicenter, Single-Arm, Open-Label Phase I Clinical Study of Pelareorep With Paclitaxel in Advanced or Metastatic Breast Cancer
• Brief Summary: This ia a multicenter, Single-Arm, Open-Label Phase I Clinical Study Evaluating the Safety and Tolerability of Pelareorep Combined with Paclitaxel Injection and the Intracorporal Process of Pelareorep in Chinese Patients with Advanced or Metastatic Breast Cancer.
• Detailed Description: This study will enroll patients with advanced or metastatic breast cancer to assess the safety and tolerability of Pelareorep at 1.5×10^10, 3.0×10^10, 4.5×10^10 (TCID50) combined with paclitaxel to fix the MTD or RP2D.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Breast Cancer

Intervention

Drug: Pelareorep

Pelareorep at 1.5×10^10 TCID50, 3×10^10 TCID50, 4.5×10^10 TCID50 on Day 1/2/8/9/15/16 with Paclitaxel at 80 mg/m^2 on Day 1/8/15 per cycle

Other Name: Paclitaxel

Study Arms

Experimental: Patients With Advanced or Metastatic Breast Cancer

Patients will receive Pelareorep with Paclitaxel for 8 cycles (28 days/cycle).

Intervention: Drug: Pelareorep

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2022): 15
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 30, 2023
• Actual Primary Completion Date: September 29, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Subjects are eligible to be included in the study only if all of the following criteria apply:

1. Voluntarily participating in this trial and having signed the Informed Consent Form (ICF).
2. Women aged ≥18 and ≤70 years (at the time of signing ICF).
3. Pathohistologically or cytologically documented unresectable advanced or metastatic breast cancer that is suitable for paclitaxel treatment, negative for HER2 amplification/overexpression as defined per the American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines (Appendix 1), and positive for estrogen receptor (ER) or progesterone receptor (PR).
4. At least one measurable target lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
5. Anticipated life expectancy ≥3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance score (PS) 0 to 1.

7. Prior chemotherapy meeting the followings:

   • The subject has received no or only 1 chemotherapy regimen (monotherapy or combined treatment) after relapse or metastasis;
   • Prior adjuvant, neoadjuvant or first-line chemotherapy with taxanes, if any, has been discontinued for >12 months by the time of enrollment, and none of the prior therapies were discontinued due to progressive disease or toxicity.

8. Prior endocrinotherapy meeting the followings:

   The subject has received at least one endocrinotherapy regimen, alone or combined with CDK4/6 or mTOR inhibitors, and has experienced progressive disease or intolerability.

9. Meeting the following criteria for laboratory tests (provided that there was no blood transfusion, use of G-CSF or use of drug for correction of, e.g., blood components, etc., within 14 days prior to the test):

   Test Criterion Hematology Neutrophil count ≥ 1.5 ×10^9/L

   Platelet count ≥ 100 ×10^9/L RBC count ≥ 90g/L Lymphocyte count ≥0.8×10^9/L Biochemistry

   Serum creatinine ≤1.5 × upper limit of normal (ULN) and estimated creatinine clearance ≥40 mL/min (by Cockcroft -Gault formula, see Appendix 3) Albumin ≥30g/L Total bilirubin ≤1.5 × ULN

   AST and ALT ≤ 2.5 × ULN (or ≤3.0 × ULN in the presence of documented liver metastasis) Coagulation International Normalized Ratio (INR) or prothrombin time (PT)

   • 1.5 × ULN Activated partial thromboplastin time (aPTT)
   • 1.5 × ULN Urinalysis (24h urine protein quantitation if necessary) Urine protein ≤1+; if ≥2+, 24h protein quantitation is required and should be <1.0g/24h

10. Duration from the end of last non-study treatment to the first study treatment:

    • Prior chemotherapy or other investigational product: >4 weeks or >5 half lives, whichever occurred later (or >4 weeks if the half life is unavailable)
    • Surgical treatment or radiotherapy: >3 weeks
    • Endocrinotherapy or small-molecular targeted therapy: >2 weeks
11. Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first study treatment, be willing to use appropriate and reliable contraception throughout the treatment period and for 6 months after last study treatment, and be willing to undergo additional pregnancy tests during the study.

Exclusion Criteria:

1. A history of other malignancies, except for adequately treated non-melanoma skin cancer or solid tumors curatively treated with no evidence of disease for > 3 years.
2. Known active, uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with CNS metastases treated with radiation therapy (WBXRT or SRS) are eligible if > 28 days following completion of XRT, they show stable disease on post-treatment MRI/CT, are off corticosteroids, and are neurologically stable.
3. Patients who have not recovered from acute toxicities of previous therapy(ies), except treatment-related alopecia or stable sensory neuropathy ≤ Grade 2 (CTCAE v5.0).
4. Systemic immunosuppressive therapy lasting >2 weeks within 1 month prior to the first study treatment or immunosuppressants used within the last 7 days including but not limited to prednisone >10 mg/day or equivalent, yet excluding intermittently used inhaled corticosteroids as bronchodilators or topical steroid injections.
5. Positivity for hepatitis B surface antigen (HBsAg) with hepatitis B viral load (HBV-DNA) higher than the laboratory lower limit of detection, or positivity for anti-hepatitis C virus antibody (anti-HCV) with hepatitis C viral load (HCV-RNA) higher than the laboratory lower limit of detection, or positivity for anti-human immunodeficiency virus (HIV) antibody (anti-HIV), or positivity for treponema pallidum antibody.
6. Patients with autoimmune diseases.
7. A history of opportunistic infection within 1 year, presence of active, uncontrolled infection (clinically significant viral, bacterial, fungal or other infections), antibiotic or antiviral treatment given within 14 days prior to first study treatment.
8. Inoculation with live or attenuated virus vaccine within 1 months prior to screening.

9. Cardiovascular diseases of clinical significance, including:

   • Myocardial infarction within the last 6 months
   • Unstable angina (despite the attempt to control it with drug)
   • Heart failure (New York Heart Association [NYHA] ≥ class II)
   • QTc interval ≥470ms (Fridericia's Correction Formula: QTcF= QT msec/(RR sec)0.33)
   • Left ventricular ejection fraction (LVEF) measured by echocardiography or multigated acquisition (MUGA) ≤50%
   • Uncontrolled hypertension (BP>150/90mmHg despite optimal treatment)
10. Severe hematological, gastrointestinal, respiratory or endocrine disorders.
11. Known hypersensitivity to paclitaxel or any of its excipients , or to Pelareorep or any of its components.
12. Patients who have been enrolled into another clinical study of drugs, medical devices or prosthesis implantation, or where ≤4 weeks have elapsed since discontinuation of another investigational drug or medical device or prosthesis implantation.
13. Pregnant or lactating women.
14. Other circumstances that in the investigator's opinion may affect patient's protocol compliance or evaluation of study indicators and thus make it inappropriate for the patient to participate in the study.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05519059
• Other Study ID Numbers: REO 026-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Adlai Nortye Biopharma Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Adlai Nortye Biopharma Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Wei Li, M.D.; The First Hospital of Jilin University

• PRS Account: Adlai Nortye Biopharma Co., Ltd.
• Verification Date: August 2022