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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Choline 300mg tid or 500mg bid, p.o
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)
Fudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGObjective Response Rate (ORR)
Time frame: 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
Disease Control Rate (DCR)
Time frame: 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
Safety and treatment-related AEs
Time frame: Randomization to death from any cause, through the end of study,assessed up to 12 months
Biomarker analysis1
Mast cell function will be measured in pretreatment tissues to predict therapy response.
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis2
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
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis3
The quantity and function of innate lympoid cells will be measured in tissues and/or peripheral blood before and after treatment
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
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Efavirenz 600mg qd, p.o
4.8mg/kg q3w
6mg/kg q3w
1200mg q3w
Mecapegfilgrastim, 6mg, d3, q3w, s.c.
AK131, 40mg/kg i.v., q2w
Theophylline, 100mg bid, p.o.