Clinical trial NCT05918133: A Study of PM8002 Plus Nab-paclitaxel as First Line Therapy for TNBC
Official title: A Phase Ib/II Study of PM8002 Injection Plus Nab-paclitaxel as First Line Therapy for Unresectable, Locally Advanced or Metastatic Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: TNBC
Keywords: First line
Lead sponsor: Biotheus Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Here, the investigators present the results from a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in subjects with locally advanced or metastatic triple negative breast cancer without previous systematic treatment.

Detailed description: PD-L1 and VEGF play important roles in immune escape and tumor angiogenesis and enhance cancer growth and metastasis. PM8002 is a bispecific antibody targeting PD-L1 and VEGF-A. Here, the investigators present the results from a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in subjects with locally advanced or metastatic triple negative breast cancer without previous systematic treatment.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily participate in clinical research; fully understand the study and voluntarily sign the informed consent; willing to follow and have the ability to complete all trial procedures;
2. Male or female, aged 18 to 75 years (including boundary value);
3. Unresectable locally advanced or metastatic breast cancer confirmed by histology or cytology, ER, PR, HER-2 are all negative. Negative ER and PR were defined as: IHCER \< 1%, IHCPR \< 1%. HER-2 negative is defined as: IHCHER-2 (-) or (1+), HER-2 (2+) must be tested by FISH and the result is negative.
4. Patients who have not received systemic treatment for advanced TNBC in the past are allowed to use taxane anti-tumor therapy in the previous neoadjuvant and/or adjuvant treatment stage, but must meet the end time of taxane neoadjuvant and/or adjuvant treatment Recurrence/metastasis interval ≥ 12 months;
5. Sufficient organ function;
6. The Eastern Cooperative Oncology Group (ECOG) score of physical status is 0-1;
7. Expected survival period ≥ 12 weeks;
8. According to the RECIST1.1 standard, the subject has at least one measurable tumor lesion.

Exclusion Criteria:

1. History of severe allergic diseases, allergic history of serious drugs (including unlisted test drugs) or known allergic to any component of this test drug;
2. Previously received any antibody or inhibitor therapy targeting PD-1/PD-L1 or VEGF;
3. There is meningeal metastasis, uncontrollable or symptomatic central nervous system (CNS) metastasis;
4. Those who have active infection and currently need intravenous anti-infection treatment;
5. At present, there are uncontrollable pleural effusion, pericardium effusion and abdominal effusion;
6. Before the start of the study and treatment, fever of unknown cause \> 38.5°C (according to the researcher's judgment, fever caused by tumor can be included in the group);
7. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
8. Known history of alcohol abuse, psychotropic substance abuse or drug abuse;
9. Have a clear history of neurological or mental disorders, such as epilepsy, dementia and schizophrenia;
10. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS);
11. Syphilis nonspecific antibody test is positive (such as TRUST and PRP) or syphilis specific antibody test is positive (such as TPPA) \[it is acceptable that "Syphilis specific antibody test" is positive but "Syphilis nonspecific antibody test" is negative for more than one year\];
12. Active tuberculosis, or a history of tuberculosis infection in the past but failed to control after treatment;
13. Active hepatitis B (HBsAg positive and HBV-DNA ≥1 1000 IU/ml) can be controlled by antiviral drugs (HBV-DNA \< 1000 IU/ml). Active hepatitis C (HCV-RNA \> detection limit of research center);
14. According to the researcher's judgment, the subject's basic illness may increase the risk of receiving the study drug, or confuse the explanation of the toxic reaction and AE;
15. It is expected that any other form of anti-tumor drug treatment will be required during the study;
16. Women who are pregnant or breastfeeding.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to approximately 2 years
measure: Treatment related adverse events (TRAEs)
timeFrame: Up to 30 days after last treatment]
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Up to approximately 2 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 2 years
measure: Progression free survival (PFS)
timeFrame: : Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Nanchang Third Hospital
state: Jiangxi
city: Jinan
country: China
facility: The first ward of breast Surgery, Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Yibin
country: China
facility: Yibin Second People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tian Jin Medicial University Cancer Institute&Hospital
state: Tianjin
Study officials:
affiliation: Fudan University
name: Wu Jiong
role: PRINCIPAL_INVESTIGATOR
References: