Triple-negative Breast CancerPhase 2RenaissanceNCT05076682
Reverse Triple Negative Immune Resistant Breast Cancer
A Phase 2 study testing Choline, anti-PD-1 antibody and chemotherapy and Sodium Cromoglicate in people with Triple-negative Breast Cancer, run by Fudan University at 1 site in China.
Trial summary
This is a Phase II, open-label, nine-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline, mifepristone) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Triple-negative Breast Cancer
- What is being tested?
- Choline, anti-PD-1 antibody and chemotherapy and Sodium Cromoglicate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 30 Jun 2022to 31 Mar 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, 200032
Zhonghua Wang, Professor, +8664175590 ext. 88807, zhonghuawang95@hotmail.com
Yin Liu, Doctor, +8664175590 ext. 88603, liuyinfudan@163.com
About this study
This is a Phase II, open-label, nine-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline, mifepristone) with immune checkpoint inhibitor or immune checkpoint inhibitor rechallenge(AK131) in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.
Read the detailed description
This is a Phase II, open-label, nine-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, efavirenz, SHR 1811, SHR 2102, mecapegfilgrastim, theophylline, mifepristone) 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, mifepristone 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
- Triple-negative Breast Cancer
- Being tested
- Choline, anti-PD-1 antibody and chemotherapy, Sodium Cromoglicate, Efavirenz, SHR-A1811
- Keywords
- TNBC, molecular subtype, precision Treatment, immunotherapy, choline, sodium cromoglicate, efavirenz
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholineDrug
Choline 300mg tid or 500mg bid, p.o
anti-PD-1 antibody and chemotherapyDrug
PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)
Sodium CromoglicateDrug
Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)
EfavirenzDrug
Efavirenz 600mg qd, p.o
SHR-A1811Drug
4.8mg/kg q3w
SHR-A2102Drug
6mg/kg q3w
SHR-1316Drug
1200mg q3w
MecapegfilgrastimDrug
Mecapegfilgrastim, 6mg, d3, q3w, s.c.
AK131Drug
AK131, 40mg/kg i.v., q2w
TheophyllineDrug
Theophylline, 100mg bid, p.o.
MifepristoneDrug
Mifepristone, 200mg, qd, d1-3, qw, p.o.
| Study group | Role | What they receive |
|---|---|---|
| Choline | Experimental | Choline with anti-PD-1 immunotherapy Receives: Drug: Choline; Drug: anti-PD-1 antibody and chemotherapy |
| Sodium cromoglicate | Experimental | Sodium cromoglicate with anti-PD-1 immunotherapy Receives: Drug: anti-PD-1 antibody and chemotherapy; Drug: Sodium Cromoglicate |
| Efavirenz | Experimental | Efavirenz with anti-PD-1 immunotherapy Receives: Drug: anti-PD-1 antibody and chemotherapy; Drug: Efavirenz |
| HER2 low | Experimental | HER2 low expression Receives: Drug: SHR-A1811; Drug: SHR-1316 |
| HER2 0 | Experimental | HER2 0 expression Receives: Drug: SHR-A2102; Drug: SHR-1316 |
| AK131 | Experimental | AK131(CD73/PD1 bispecific antibody) Receives: Drug: AK131 |
| Mecapegfilgrastim | Experimental | Mecapegfilgrastim with anti-PD-1 immunotherapy Receives: Drug: anti-PD-1 antibody and chemotherapy; Drug: Mecapegfilgrastim |
| Theophylline | Experimental | Theophylline with anti-PD-1 immunotherapy Receives: Drug: Theophylline |
| Mifepristone | Experimental | Mifepristone with anti-PD-1 immunotherapy Receives: Drug: anti-PD-1 antibody and chemotherapy; Drug: Mifepristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Measured: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Immune changes in peripheral blood
Measured: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Secondary outcomes (6)
Disease Control Rate (DCR)
Measured: Baseline through end of study, assessed up to 6 months
Progression Free Survival (PFS)
Measured: Randomization to death from any cause, through the end of study,assessed up to 6 months
Safety and treatment-related AEs
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start30 Jun 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Triple-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
- Investigators
- Zhimin Shao, Professor, Principal investigator, Fudan U
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076682
- Sponsor's protocol ID
- 2107239-9
- Acronym
- Renaissance
- Status last verified
- Oct 2026
- First submitted
- 12 Sep 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40563015