Reverse Triple Negative Immune Resistant Breast Cancer (Renaissance)

November 25, 2025 updated by: Zhimin Shao, Fudan University
This is a Phase II, open-label, seven-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II, open-label, three-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during or following previous immune checkpoint inhibitors. The investigators have achieved a breakthrough in the FUTURE study with an ORR (objective response rate) reaching 52.6% in IM (immunomodulatory) subtype TNBC patients. Despite this, there are still some IM subtype patients resistant to immunotherapy. How to reverse immunotherapy resistance or how to increase the sensitivity of immunotherapy efficacy, has become an urgent clinical problem to be solved. The preclinical results of our center show that sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, AK131, theophylline play a potentially important role in regulating the tumor immune microenvironment and can inhibit the growth of tumors in mice, and enhance the efficacy of PD-1 inhibitors in mice. Based on preclinical studies, the investigators designed this study to enroll mTNBC patients who have progressed during or following immunotherapy, and to explore the efficacy of these drugs at a clinical level, providing new strategies of combined treatment for TNBC patients.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ECOG Performance Status of 0, 1, or 2
  • Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
  • Radiologic/objective evidence of recurrence or disease progression after immunotherapy(combined with targeted therapy or chemo ) for metastatic breast cancer(MBC)
  • Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
  • have the cognitive ability to understand the protocol and be willing to participate and to be followed up.

Exclusion Criteria:

  • Symptomatic, untreated, or actively progressing CNS metastases
  • Active or history of autoimmune disease or immune deficiency
  • Significant cardiovascular disease
  • History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
  • Treatment with chemotherapy, radiotherapy,immunotherapy or surgery (outpatient clinic surgery excluded) within 3 weeks prior to initiation of study treatment.
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
  • History of allergies to the drug components of this trial
  • History of eosinophilosis or mastocytosis
  • Patients who have been using oral steroid hormones for a long time will need to stop for 4 weeks if they have used them occasionally in the past
  • For the Mecapegfilgrastim group, patients had previously received PEG-rhG-CSF in combination with immunotherapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Choline
Choline with anti-PD-1 immunotherapy
Drug: Choline
Choline 300mg tid or 500mg bid, p.o
Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Experimental: Sodium cromoglicate
Sodium cromoglicate with anti-PD-1 immunotherapy
Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Drug: Sodium Cromoglicate
Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)
Experimental: Efavirenz
Efavirenz with anti-PD-1 immunotherapy
Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Drug: Efavirenz
Efavirenz 600mg qd, p.o
Experimental: HER2 low
HER2 low expression
Drug: SHR-A1811
4.8mg/kg q3w
Drug: SHR-1316
1200mg q3w
Experimental: HER2 0
HER2 0 expression
Drug: SHR-1316
1200mg q3w
Drug: SHR-A2102
6mg/kg q3w
Experimental: AK131
AK131(CD73/PD1 bispecific antibody)
Drug: AK131
AK131, 40mg/kg i.v., q2w
Experimental: Mecapegfilgrastim
Mecapegfilgrastim with anti-PD-1 immunotherapy
Drug: anti-PD-1 antibody and chemotherapy
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Drug: Mecapegfilgrastim
Mecapegfilgrastim, 6mg, d3, q3w, s.c.
Experimental: Theophylline
Theophylline with anti-PD-1 immunotherapy
Drug: Theophylline
Theophylline, 100mg bid, p.o.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate (ORR)
Time Frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Immune changes in peripheral blood
Time Frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: Baseline through end of study, assessed up to 6 months
Baseline through end of study, assessed up to 6 months
Progression Free Survival (PFS)
Time Frame: Randomization to death from any cause, through the end of study,assessed up to 6 months
Randomization to death from any cause, through the end of study,assessed up to 6 months
Safety and treatment-related AEs
Time Frame: Randomization to death from any cause, through the end of study,assessed up to 12 months
Randomization to death from any cause, through the end of study,assessed up to 12 months
Biomarker analysis1
Time Frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Mast cell function will be measured in pretreatment tissues to predict therapy response.
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis2
Time Frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Immunohistochemical staining of pre- and post-treatment tissue sections was carried out to evaluate PD-L1 expression, mast cell function, innate lymphoid cell porprotion and activity, and overall inflammatory status
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis3
Time Frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
The quantity and function of innate lympoid cells will be measured in tissues and/or peripheral blood before and after treatment
Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Zhimin Shao, Professor, Fudan U

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2022

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

September 12, 2021

First Submitted That Met QC Criteria

September 29, 2021

First Posted (Actual)

October 13, 2021

Study Record Updates

Last Update Posted (Estimated)

December 3, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2107239-9

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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