Reverse Triple Negative Immune Resistant Breast Cancer (Renaissance)

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Triple-negative Breast Cancer

Treatments: Drug: Mecapegfilgrastim; Drug: Theophylline; Drug: AK131; Drug: SHR-A1811; Drug: Sodium Cromoglicate; Drug: Efavirenz; Drug: SHR-A2102; Drug: anti-PD-1 antibody and chemotherapy; Drug: SHR-1316; Drug: Choline

Study type: Interventional

Funder types: Other

Identifiers

NCT05076682

2107239-9

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 8 patient groups

Choline

Experimental group

Description:

Choline with anti-PD-1 immunotherapy

Treatment:

Drug: Choline

Drug: anti-PD-1 antibody and chemotherapy

Sodium cromoglicate

Experimental group

Description:

Sodium cromoglicate with anti-PD-1 immunotherapy

Treatment:

Drug: anti-PD-1 antibody and chemotherapy

Drug: Sodium Cromoglicate

Efavirenz

Experimental group

Description:

Efavirenz with anti-PD-1 immunotherapy

Treatment:

Drug: anti-PD-1 antibody and chemotherapy

Drug: Efavirenz

HER2 low

Experimental group

Description:

HER2 low expression

Treatment:

Drug: SHR-1316

Drug: SHR-A1811

HER2 0

Experimental group

Description:

HER2 0 expression

Treatment:

Drug: SHR-1316

Drug: SHR-A2102

AK131

Experimental group

Description:

AK131(CD73/PD1 bispecific antibody)

Treatment:

Drug: AK131

Mecapegfilgrastim

Experimental group

Description:

Mecapegfilgrastim with anti-PD-1 immunotherapy

Treatment:

Drug: anti-PD-1 antibody and chemotherapy

Drug: Mecapegfilgrastim

Theophylline

Experimental group

Description:

Theophylline with anti-PD-1 immunotherapy

Treatment:

Drug: Theophylline