Reverse Triple Negative Immune Resistant Breast Cancer

NCT ID: NCT05076682

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-30

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Triple-negative Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Choline

Choline with anti-PD-1 immunotherapy

Group Type EXPERIMENTAL

Choline

Intervention Type DRUG

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

anti-PD-1 antibody and chemotherapy

Intervention Type DRUG

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

Sodium cromoglicate

Sodium cromoglicate with anti-PD-1 immunotherapy

Group Type EXPERIMENTAL

anti-PD-1 antibody and chemotherapy

Intervention Type DRUG

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

Sodium Cromoglicate

Intervention Type DRUG

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

Efavirenz

Efavirenz with anti-PD-1 immunotherapy

Group Type EXPERIMENTAL

anti-PD-1 antibody and chemotherapy

Intervention Type DRUG

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

Efavirenz

Intervention Type DRUG

Efavirenz 600mg qd, p.o

HER2 low

HER2 low expression

Group Type EXPERIMENTAL

SHR-A1811

Intervention Type DRUG

4.8mg/kg q3w

SHR-1316

Intervention Type DRUG

1200mg q3w

HER2 0

HER2 0 expression

Group Type EXPERIMENTAL

SHR-A2102

Intervention Type DRUG

6mg/kg q3w

SHR-1316

Intervention Type DRUG

1200mg q3w

AK131

AK131(CD73/PD1 bispecific antibody)

Group Type EXPERIMENTAL

AK131

Intervention Type DRUG

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

Mecapegfilgrastim

Mecapegfilgrastim with anti-PD-1 immunotherapy

Group Type EXPERIMENTAL

anti-PD-1 antibody and chemotherapy

Intervention Type DRUG

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

Mecapegfilgrastim

Intervention Type DRUG

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

Theophylline

Theophylline with anti-PD-1 immunotherapy

Group Type EXPERIMENTAL

Theophylline

Intervention Type DRUG

Theophylline, 100mg bid, p.o.

Interventions

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Choline

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

Intervention Type 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)

Intervention Type DRUG

Sodium Cromoglicate

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

Intervention Type DRUG

Efavirenz

Efavirenz 600mg qd, p.o

Intervention Type DRUG

SHR-A1811

4.8mg/kg q3w

Intervention Type DRUG

SHR-A2102

6mg/kg q3w

Intervention Type DRUG

SHR-1316

1200mg q3w

Intervention Type DRUG

Mecapegfilgrastim

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

Intervention Type DRUG

AK131

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

Intervention Type DRUG

Theophylline

Theophylline, 100mg bid, p.o.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Zhimin Shao

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Zhimin Shao, Professor

Role: PRINCIPAL_INVESTIGATOR

Fudan U

Locations

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Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Zhimin Shao, Professor

Role: CONTACT

08664175590 ext. 88807

Zhonghua Wang, Professor

Role: CONTACT

08664175590 ext. 88807

Facility Contacts

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Zhonghua Wang, Professor

Role: primary

+8664175590 ext. 88807

Yin Liu, Doctor

Role: backup

+8664175590 ext. 88603

References

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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.

Reference Type DERIVED
PMID: 40563015 (View on PubMed)

Other Identifiers

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2107239-9

Identifier Type: -

Identifier Source: org_study_id

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