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
- Are there results?
- Not yet: the study is under way
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
Show all 10Show fewer
- 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
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reverse Triple Negative Immune Resistant Breast Cancer
- ClinicalTrials.gov ID
- NCT05076682
- Acronym / sponsor ID
- Renaissance / 2107239-9
- Conditions
- Triple-negative Breast Cancer
- Keywords
- TNBC, molecular subtype, precision Treatment, immunotherapy, choline, sodium cromoglicate, efavirenz
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 30 Jun 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 13 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Choline | Experimental | Drug: Choline, Drug: anti-PD-1 antibody and chemotherapyCholine with anti-PD-1 immunotherapy |
| Sodium cromoglicate | Experimental | Drug: anti-PD-1 antibody and chemotherapy, Drug: Sodium CromoglicateSodium cromoglicate with anti-PD-1 immunotherapy |
| Efavirenz | Experimental | Drug: anti-PD-1 antibody and chemotherapy, Drug: EfavirenzEfavirenz with anti-PD-1 immunotherapy |
| HER2 low | Experimental | Drug: SHR-A1811, Drug: SHR-1316HER2 low expression |
| HER2 0 | Experimental | Drug: SHR-A2102, Drug: SHR-1316HER2 0 expression |
| AK131 | Experimental | Drug: AK131AK131(CD73/PD1 bispecific antibody) |
| Mecapegfilgrastim | Experimental | Drug: anti-PD-1 antibody and chemotherapy, Drug: MecapegfilgrastimMecapegfilgrastim with anti-PD-1 immunotherapy |
| Theophylline | Experimental | Drug: TheophyllineTheophylline with anti-PD-1 immunotherapy |
| Mifepristone | Experimental | Drug: anti-PD-1 antibody and chemotherapy, Drug: MifepristoneMifepristone with anti-PD-1 immunotherapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CholineCholine 300mg tid or 500mg bid, p.o | Drug | Choline |
| anti-PD-1 antibody and chemotherapyPD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment) | Drug | Choline, Efavirenz, Mecapegfilgrastim, Mifepristone, Sodium cromoglicate |
| Sodium CromoglicateSodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray) | Drug | Sodium cromoglicate |
| EfavirenzEfavirenz 600mg qd, p.o | Drug | Efavirenz |
| SHR-A18114.8mg/kg q3w | Drug | HER2 low |
| SHR-A21026mg/kg q3w | Drug | HER2 0 |
| SHR-13161200mg q3w | Drug | HER2 0, HER2 low |
| MecapegfilgrastimMecapegfilgrastim, 6mg, d3, q3w, s.c. | Drug | Mecapegfilgrastim |
| AK131AK131, 40mg/kg i.v., q2w | Drug | AK131 |
| TheophyllineTheophylline, 100mg bid, p.o. | Drug | Theophylline |
| MifepristoneMifepristone, 200mg, qd, d1-3, qw, p.o. | Drug | Mifepristone |
Primary outcome
Objective 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
6 secondary outcomes
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
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis2
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Biomarker analysis3
Time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2026.
- Derived from this study: PubMed 40563015Wu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhimin Shao, Professor principal investigator
Fudan U
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhimin Shao, Professor (08664175590 ext. 88807, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Baseline until disease progression or loss of clinical benefit, assessed up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05076682, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2026.