A Multicohort Study of Toripalimab in Combination With Investigator-Selected Chemotherapy for Advanced HER2-Negative Breast Cancer (2025-370)

To evaluate the efficacy and safety of toripalimab in combination with investigator-selected chemotherapy in patients with recurrent or metastatic HER2-negative breast cancer who have failed prior systemic therapy.

Study Overview

• Status: Recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: Toripalimab; Drug: TPC

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Yan, Chief physician; Phone Number: +86-15713857388; Email: ym200678@126.com
• Study Contact Backup: Name: Meng wei Zhang, Associate Chief Physician

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Min Yan, Chief physician; Phone Number: +86-15713857388; Email: ym200678@126.com
      • Principal Investigator: Min Yan, Chief physician
      • Contact: Meng wei Zhang, Associate Chief Physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary participation: the subject must give written informed consent, be compliant, and agree to attend all follow-up visits.
2. Age ≥ 18 years.
3. ECOG performance-status score ≤ 1 and life expectancy ≥ 3 months.
4. Histologically or cytologically confirmed HER2-negative breast cancer (HER2-negative is defined as either IHC 0, IHC 1+, or IHC 2+ with a negative in-situ-hybridisation [ISH] result).

5. For subjects with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC):

   - Must have experienced progression during/after at least one prior systemic regimen for recurrent/metastatic disease (recurrence ≤ 12 months after neoadjuvant/adjuvant therapy counts as first-line failure).

   - Cohort assignment by prior immune-checkpoint-inhibitor (ICI) exposure:

   1. Cohort A - ICI-pretreated:

      • If ICI was given in adjuvant setting, recurrence must occur ≥ 12 months after completion of immunotherapy.
      • If ICI was given in neoadjuvant or metastatic setting, best overall response must have met clinical-benefit criteria (PR, CR, or SD > 24 weeks).
   2. Cohort B - ICI-naïve: no prior anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any other antibody targeting T-cell co-stimulatory or checkpoint pathways.

6. For subjects with hormone-receptor-positive (HR+) breast cancer:

   • Must have progressed after ≥ 2 prior endocrine regimens in the recurrent/metastatic setting (unless investigator judges no endocrine benefit), and
   • Must have progressed after ≥ 1 prior systemic chemotherapy for recurrent/metastatic disease (recurrence ≤ 12 months after adjuvant/neoadjuvant therapy counts as first-line failure).
7. At least one measurable lesion per RECIST v1.1.

8. Adequate organ function, defined as:

   Haematology (no transfusion within 14 days):

   1. Haemoglobin ≥ 9 g/dL
   2. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
   3. Platelet count ≥ 100 × 10⁹/L . Serum chemistry:
   1. Total bilirubin ≤ 1.5 × ULN, or if total bilirubin > ULN then direct bilirubin ≤ ULN
   2. ALT and AST ≤ 2.5 × ULN
   3. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min
9. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before first dose and must use highly effective contraception from first dose until 6 months after last dose.

WOCBP is defined as any sexually mature female who has not undergone hysterectomy or bilateral oophorectomy and who has not experienced natural amenorrhoea for ≥ 24 consecutive months (including women with treatment-induced amenorrhoea).Men whose partners are WOCBP must also use effective contraception during the same period.

Exclusion Criteria:

1. Uncontrolled central-nervous-system metastases (symptomatic or requiring corticosteroids or mannitol for symptom control).
2. Clinically significant or uncontrolled cardiac disease within 6 months before first dose, including congestive heart failure, angina, myocardial infarction, or ventricular arrhythmia.
3. Malignancy within 5 years before first dose, except adequately treated basal-cell carcinoma of the skin or carcinoma in situ of the cervix.
4. Active autoimmune disease requiring systemic therapy within 2 years before first dose, except vitiligo, type-1 diabetes, or residual hypothyroidism due to autoimmune thyroiditis managed with hormone replacement only.
5. Uncontrolled pleural, pericardial, or ascitic fluid requiring repeated drainage.
6. Documented human immunodeficiency virus (HIV) infection.
7. Documented hepatitis-B infection or active hepatitis-C infection.
8. Prior hypersensitivity to any component or excipient of the investigational product(s).
9. Any condition judged by the investigator to render the patient unsuitable for trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Cohort A: triple-negative breast cancer (TNBC) previously treated with immune-checkpoint inhibitors (ICI);	Drug: Toripalimab; Toripalimab; Drug: TPC; Treatment of Physician's Choice
Experimental: Cohort B; Cohort B: TNBC without prior ICI exposure;	Drug: Toripalimab; Toripalimab; Drug: TPC; Treatment of Physician's Choice
Experimental: Cohort C; Cohort C: HR-positive/HER2-negative breast cancer.	Drug: Toripalimab; Toripalimab; Drug: TPC; Treatment of Physician's Choice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR by investigator	ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1.	At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	OS is the time from the date of first dose until the date of death by any cause.	up to 3 years
DoR	DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.	up to 3 years
PFS	PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).	up to 3 years
Safety (Proportion of AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experienced an adverse event and discontinued study drug due to an AE.	from time of informed consent provided to 30 days after the last dose of study therapy
DCR	DCR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1.	At baseline, at the time point of every 8 weeks within first 24 weeks, thereafter every 12 weeks

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Min Yan, Chief physician, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: December 30, 2025
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: toripalimab
• Other Study ID Numbers: 2025-370

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No