Reverse Triple Negative Immune Resistant Breast Cancer

Phase 2

Recruiting

• Conditions: Triple-negative Breast Cancer
• Interventions: Drug: Choline; Drug: SHR-A1811; Drug: SHR-A2102; Drug: AK131; Drug: anti-PD-1 antibody and chemotherapy; Drug: Sodium Cromoglicate; Drug: Efavirenz; Drug: SHR-1316; Drug: Mecapegfilgrastim

• Registration Number: NCT05076682
• Lead Sponsor: Fudan University

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) 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

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 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 Timeline

• Study First Submitted: 2021-09-12
• Study First Submitted QC: 2021-09-29
• Study First Posted: 2021-10-13
• Study Start: 2022-06-30
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-22
• Last Update Posted: 2025-07-28
• Primary Completion: 2026-12-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Choline	Choline	Choline with anti-PD-1 immunotherapy
Choline	anti-PD-1 antibody and chemotherapy	Choline with anti-PD-1 immunotherapy
Sodium cromoglicate	anti-PD-1 antibody and chemotherapy	Sodium cromoglicate with anti-PD-1 immunotherapy
Sodium cromoglicate	Sodium Cromoglicate	Sodium cromoglicate with anti-PD-1 immunotherapy
Efavirenz	anti-PD-1 antibody and chemotherapy	Efavirenz with anti-PD-1 immunotherapy
Efavirenz	Efavirenz	Efavirenz with anti-PD-1 immunotherapy
HER2 low	SHR-A1811	HER2 low expression
HER2 low	SHR-1316	HER2 low expression
HER2 0	SHR-A2102	HER2 0 expression
HER2 0	SHR-1316	HER2 0 expression
AK131	AK131	AK131(CD73/PD1 bispecific antibody)
Mecapegfilgrastim	anti-PD-1 antibody and chemotherapy	Mecapegfilgrastim with anti-PD-1 immunotherapy
Mecapegfilgrastim	Mecapegfilgrastim	Mecapegfilgrastim with anti-PD-1 immunotherapy

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 analysis2	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
Biomarker analysis3	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
Biomarker analysis1	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.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China