Reverse Triple Negative Immune Resistant Breast Cancer

NCT05076682 | Recruiting Phase 2

• 1 other identifier: 2107239-9
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple-negative Breast Cancer

Keywords

TNBC; molecular subtype; precision Treatment; immunotherapy; choline; sodium cromoglicate; efavirenz

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

• Immune changes in peripheral blood

  Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Secondary Outcomes (6)

• Disease Control Rate (DCR)

  Baseline through end of study, assessed up to 6 months

• Progression Free Survival (PFS)

  Randomization to death from any cause, through the end of study,assessed up to 6 months

• Safety and treatment-related AEs

  Randomization to death from any cause, through the end of study,assessed up to 12 months

• Biomarker analysis1

  Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

• Biomarker analysis2

  Baseline until disease progression or loss of clinical benefit, assessed up to 6 months

Study Arms (8)

Choline

EXPERIMENTAL

Choline with anti-PD-1 immunotherapy

Drug: Choline; Drug: anti-PD-1 antibody and chemotherapy

Sodium cromoglicate

EXPERIMENTAL

Sodium cromoglicate with anti-PD-1 immunotherapy

Drug: anti-PD-1 antibody and chemotherapy; Drug: Sodium Cromoglicate

Efavirenz

EXPERIMENTAL

Efavirenz with anti-PD-1 immunotherapy

Drug: anti-PD-1 antibody and chemotherapy; Drug: Efavirenz

HER2 low

EXPERIMENTAL

HER2 low expression

Drug: SHR-A1811; Drug: SHR-1316

HER2 0

EXPERIMENTAL

HER2 0 expression

Drug: SHR-A2102; Drug: SHR-1316

AK131

EXPERIMENTAL

AK131(CD73/PD1 bispecific antibody)

Drug: AK131

Mecapegfilgrastim

EXPERIMENTAL

Mecapegfilgrastim with anti-PD-1 immunotherapy

Drug: anti-PD-1 antibody and chemotherapy; Drug: Mecapegfilgrastim

Theophylline

EXPERIMENTAL

Theophylline with anti-PD-1 immunotherapy

Drug: Theophylline

Interventions

Sodium Cromoglicate DRUG

Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)

Sodium cromoglicate

Efavirenz DRUG

Efavirenz 600mg qd, p.o

Efavirenz

SHR-A1811 DRUG

4.8mg/kg q3w

HER2 low

SHR-A2102 DRUG

6mg/kg q3w

HER2 0

SHR-1316 DRUG

1200mg q3w

HER2 0; HER2 low

Mecapegfilgrastim DRUG

Mecapegfilgrastim, 6mg, d3, q3w, s.c.

Mecapegfilgrastim

AK131 DRUG

AK131, 40mg/kg i.v., q2w

AK131

Theophylline DRUG

Theophylline, 100mg bid, p.o.

Theophylline

Choline DRUG

Choline 300mg tid or 500mg bid, p.o

Choline

anti-PD-1 antibody and chemotherapy DRUG

PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)

Choline; Efavirenz; Mecapegfilgrastim; Sodium cromoglicate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

Related Publications (1)

• Wu SY, Jin X, Liu Y, Wang ZY, Zuo WJ, Ma D, Xiao Y, Fu T, Xiao YL, Chen L, Liu XY, Fan L, Wang ZH, Shen M, Liu R, Chai WJ, Shao ZM, Jiang YZ. Mobilizing antigen-presenting mast cells in anti-PD-1-refractory triple-negative breast cancer: a phase 2 trial. Nat Med. 2025 Jul;31(7):2405-2415. doi: 10.1038/s41591-025-03776-7. Epub 2025 Jun 25.

  PMID: 40563015 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Choline; Drug Therapy; Cromolyn Sodium; efavirenz; pegylated granulocyte colony-stimulating factor; Theophylline

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds; Therapeutics; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Xanthines; Alkaloids; Purinones; Purines

Study Officials

• Zhimin Shao, Professor

  Fudan U

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimin Shao, Professor

CONTACT

08664175590; zhimingshao@yahoo.com

Zhonghua Wang, Professor

CONTACT

08664175590; zhonghuawang95@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2021
• First Posted: October 13, 2021
• Study Start: June 30, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

CN (1)