Capecitabine plus pembrolizumab in patients with triple negative breast cancer after chemoimmunotherapy and surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Mar 2025 → ongoing

Decision date (initial)

2024-11-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

institutional fund (hospital clinical research program)

External identifiers

EU CT number

2023-505291-30-01

ClinicalTrials.gov

NCT05973864

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the efficacy of post-operative capecitabine added to pembrolizumab on the invasive disease-free survival (iDFS) as assessed by investigator in subjects with Triple Negative Breast Cancer and residual disease after neoadjuvant chemotherapy associated with pembrolizumab.

Secondary objectives 2

1. Efficacy: To assess the clinical impact of the capecitabine plus pembrolizumab combination in the target population and in subgroup populations according RCB score ( 25% RCB I versus 75% RCB II/III)) in terms of: a) Overall Survival (OS) b) Distant Disease Free Survival (DDFS) c) Efficacy (iDFS, OS and DDFS) of experimental arm will be compared to the external cohort of patients treated with pembrolizumab as part of standard of care after surgery, for localized TNBC without pCR after NAC.
2. Safety: To evaluate the safety profile of the capecitabine plus pembrolizumab combination according to the use of radiation (yes/no) in the target population.

Conditions and MedDRA coding

Triple Negative Breast Cancer with residual disease after neoadjuvant chemo-immunotherapy.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 22

1. Experimental arm : Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent;
2. Experimental arm : Resolution to at least grade 1 of all acute toxicities from previous therapies including immune related toxicity due to pembrolizumab, except alopecia and grade 2 immune-related endocrinopathies controlled by hormone replacement which are allowed;
3. Experimental arm : Minimal/maximal period for prior treatments (i.e. minimal delay from last dose of prior treatment to C1D1): breast surgery (the wound must have healed prior to C1D1) ≥2 weeks (maximum 10 weeks); last pembrolizumab injection ≥3 weeks;
4. Experimental arm : Women of child-bearing potential must have a negative serum pregnancy test within 7 days before C1D1;
5. Experimental arm : Women of child-bearing potential and male patients must agree to use 1 effective form of contraception from the time of the negative pregnancy test up to 4 months after the last dose of study drugs;
6. Experimental arm : Patient should be able and willing to comply with study visits and procedures as per protocol;
7. Experimental arm : Patients must be affiliated to a Social Security System (or equivalent).
8. Experimental arm : Subject ≥18 years of age on day of signing informed consent form (ICF);
9. Experimental arm : Histologically proven TNBC defined as follows: a. HER2 negativity (ASCO/CAP criteria) b. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;
10. Experimental arm : TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin). Other drugs may be acceptable following discussion with the sponsor (with the exclusion of capecitabine);
11. Experimental arm : Complete resection of the breast tumor(s) (and of any invaded lymph node);
12. Experimental arm : No complete pathological response, defined as RCB Class I, II or III (per local assessment);
13. Experimental arm : Available representative formalin-fixed paraffin-embedded (FFPE) tumor block from surgery specimen with its histological report;
14. Experimental arm : Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;
15. Experimental arm : Adequate organ and bone marrow function. All screening lab tests should be performed within 28 days before randomization;
16. External Cohort : Patient information prior to study entry and non-opposition to data collection
17. External Cohort : Subject ≥18 years of age ;
18. External Cohort : Histologically proven TNBC defined as follows: a. HER2 negativity (ASCO/CAP criteria) b. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;
19. External Cohort : TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin). Other drugs may be acceptable following discussion with the sponsor (with the exclusion of capecitabine);
20. External Cohort : Complete resection of the breast tumor(s) (and of any invaded lymph node);
21. External Cohort : No complete pathological response, defined as RCB Class I, II or III (per local assessment);
22. External Cohort : Patient should have received at least one injection of pembrolizumab as post-surgery treatment (concomitantly or after radiotherapy).

Exclusion criteria 19

1. Experimental arm : Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination performed during screening period;
2. Experimental arm : Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;
3. Experimental arm : Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer or previously treated malignancy with no evidence of disease for ≥2 years;
4. Experimental arm : Presents a contraindication to continue pembrolizumab treatment as per respective SmPC including known hypersensitivity;
5. Experimental arm : Previous immune-related adverse event of any grade due to pembrolizumab that led to permanent discontinuation of pembrolizumab;
6. Experimental arm : Presents a contraindication to capecitabine treatment as per SmPC (See EMA website for most recent edition of SmPC);
7. Experimental arm : Complete DPD (Dihydropyrimidine Dehydrogenase) deficiency (a systematic screening of DPD deficiency must be performed);
8. Experimental arm : Patient with active infection ;
9. Experimental arm : Patients with history of uncontrolled or symptomatic cardiac disease ;
10. Experimental arm : Patients having received brivudine within 4 weeks prior to inclusion;
11. Experimental arm : Require the use of one of the following forbidden treatments during the study treatment period:  Any investigational anticancer therapy other than the protocol specified treatment;  Any concurrent chemotherapy, immunotherapy, biologic for cancer treatment, other than the ones stated in the protocol;
12. Experimental arm : Pregnant women or women who are breast-feeding;
13. Experimental arm : Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;
14. Experimental arm : Persons deprived of their liberty or under protective custody or guardianship;
15. Experimental arm : Participation in another therapeutic trial within the 30 days prior to randomization.
16. External Cohort : Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination after surgery.
17. External Cohort : Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;
18. External Cohort : Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer or previously treated malignancy with no evidence of disease for ≥2 years;
19. External Cohort : Any investigational anticancer therapy (chemotherapy, immunotherapy, biologic for cancer treatment) other than pembrolizumab only as adjuvant treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 2-year Invasive disease free survival (iDFS).

Secondary endpoints 4

1. Efficacy: Overall Survival (OS) is defined as the time from the date of inclusion to the date of death due to any cause. For patients alive, OS will be censored at date of last contact.
2. Efficacy: Distant disease-free survival (DDFS) is defined as the time from the date of inclusion to the date of distant relapse or death due to any cause. For patients alive without distant relapse, DDFS will be censored at date of last contact.
3. Efficacy : iDFS, OS and DDFS will also be compared to the external cohort of TNBC patients without pCR after NAC and treated with adjuvant pembrolizumab as part of standard of care after surgery
4. Safety : Safety and tolerability assessed by Adverse Events (AEs) as per the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

AIT RAHMOUNE Nourredine

Public contact point

Organisation

Unicancer

Contact name

AIT RAHMOUNE Nourredine

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications