Early Breast CancerPhase 2KEYPARTNERNCT06371807
Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab
A Phase 2 study testing Pembrolizumab injection in people with Early Breast Cancer and Triple Negative Breast Cancer, run by Fundacao Champalimaud at 3 sites in Portugal.
Trial summary
Phase II, randomized, Active-controlled open label trial for treatment of high risk, HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy on a background of pembrolizumab Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Early Breast Cancer, Triple Negative Breast Cancer
- What is being tested?
- Pembrolizumab injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 3 sitesPortugal
- Study dates
- Jul 2024to Dec 2026
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Participants are excluded from the study if any of the following criteria apply:
- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anticancer or anti-proliferative intent within the last 12 months.
Show all 23Show fewer
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has significant cardiovascular disease, such as:
- History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months
- Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has an active infection requiring systemic therapy.
- If surgery was performed prior to screening, has persistent adverse events or incomplete wound healing considered clinically relevant by the treating investigator.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 12 months after the last dose of cyclophosphamide or 6 months after last chemotherapy (whichever occurs last).
- Has had an allogenic tissue/solid organ transplant.
- Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial and to consent
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal3 sites
Fundaçao Champalimaud, Avenida Brasilia,
Lisbon, 1400-038
Ines Sousa, MSc, +351 210480048, ines.sousa@fundacaochampalimaud.pt
Fatima Cardoso, MD, +351 210480048, fatimacardoso@fundacaochampalimaud.pt
Centro Hospitalar Universitário Lisboa Norte E.P.E
Lisbon, 1649-028
Instituto Português de Oncologia Francisco Gentil, E.P.E
Porto, 4200-072
Joana Maia, 22 508 40 00 ext. 2040, joana.h.maia@ipoporto.min-saude.pt
Miguel Abreu, MD, 22 508 40 00 ext. 2040, antonio.m.abreu@ipoporto.min-saude.pt
About this study
Official title: Immunogenicity Profile of Neoadjuvant Keytruda in Combination With Anthracycline Versus Carboplatin/PAclitaxel Containing Chemotherapy Regimen for The Treatment of Early-stage, TILs-Positive, Triple-Negative Breast CanceR
Phase II, randomized, Active-controlled open label trial for treatment of high risk, HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy on a background of pembrolizumab
Read the detailed description
This is a randomized, open-label, pilot study to evaluate the existence of a differential tumor immunomodulatory profile of neoadjuvant pembrolizumab in combination with paclitaxel and carboplatin vs pembrolizumab in combination with EC/AC in patients with triple negative, tumor infiltrating lymphocytes (TILs) enriched, early breast cancer to allow the optimization of future de-escalation strategies. There will be crossover between treatment arms when moving from the neoadjuvant to adjuvant treatment period for completion of standard chemotherapy plus pembrolizumab.
The chemotherapy regimen included in this study is built upon previous studies of pembrolizumab plus chemotherapy. The synergistic effect of different chemotherapy backbone and pembrolizumab will be studied as part of a 2-arm study:
Arm 1: (KXCb - PA[E]C): Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting.
Arm 2: (KPA[E]C - KXCb): Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting.
In case of clinical evidence of non-pCR, i.e., biopsy proven residual disease after the neoadjuvant phase, patients can proceed to the crossover part of the adjuvant phase before surgery (i.e., 4 cycles of chemotherapy plus pembrolizumab) receiving the remaining administrations of pembrolizumab after surgery.
- Conditions
- Early Breast Cancer, Triple Negative Breast Cancer
- Being tested
- Pembrolizumab injection
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab injectionDrug
Also called Doxorubicin or Epirubicin, Cyclophosphamide, Paclitaxel, Carboplatin
(KXCb - PA[E]C) vs (KPA[E]C - KXCb) Pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab in the adjuvant setting vs Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab in the adjuvant setting
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: (KXCb - PA[E]C) | Active comparator | Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting. Receives: Drug: Pembrolizumab injection |
| (KPA[E]C - KXCb) | Experimental | Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting Receives: Drug: Pembrolizumab injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detect immunologic activation signal and the immunologically defined most suitable patient population for the synergistic interaction between pembrolizumab and chemotherapy backbone
Compare signals of immunological activation or a more favorable immunological context beetween T cell subpopulations and transcriptional changes of T cell populations infiltrating tumors at baseline and C2D1
Measured: At the end of cycle 1 (each cycle is 28 days)
Rate of pCR
Compare the rate of pCR in subjects with locally advanced TNBC with TILs ≥ 10% in arm A and arm B at cycle 4
Measured: 6 months to one year after subject inclusion
Primary translational endpoint
Quantification of number of T cells per mm2 with different phenotypes using fate bifurcation as defined as the proportion of TILs with the phenotype T-bet(hi) PD1(mid) CD8+.
Measured: 6 months to one year after subject inclusion
Secondary outcomes (2)
Changes in the immunogenic phenotype
Determine changes in the immunogenic phenotype by longitudinally evaluating RNA-based gene expression signatures (e.g., tumor inflammation signature expression of granzyme A [GZMA] and perforin 1 at baseline and at C2D1.
Measured: 6 months to one year after subject inclusion
Incidence of treatment relatred Adverse events
Describe the safety and tolerability of the combinations of pembrolizumab plus chemotherapy (either EC/AC or paclitaxel + carboplatin) in the Neoadjuvant and Adjuvant setting throught the CTCAE version 5.0 adverse event evaluation
Measured: 6 months to one year after subject inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study startJul 2024 (estimated)
- Primary completionJul 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early Breast CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundacao Champalimaud
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fatima Cardoso, MD, Study director, Breast Unit Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06371807
- Sponsor's protocol ID
- EU CTR n.º 2023-507008-30-00
- Acronym
- KEYPARTNER
- Status last verified
- Feb 2024
- First submitted
- 12 Mar 2024
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Primary outcome will be shared in major medical Congress
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunogenicity Profile of Neoadjuvant Keytruda in Combination With Anthracycline Versus Carboplatin/PAclitaxel Containing Chemotherapy Regimen for The Treatment of Early-stage, TILs-Positive, Triple-Negative Breast CanceR
- ClinicalTrials.gov ID
- NCT06371807
- Acronym / sponsor ID
- KEYPARTNER / EU CTR n.º 2023-507008-30-00
- Conditions
- Early Breast Cancer, Triple Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Fundacao ChampalimaudUniversity, hospital or other
- Study start
- Jul 2024 (estimated)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 17 Apr 2024 (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.
Phase II, randomized, Active-controlled open label trial for treatment of high risk, HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy on a background of pembrolizumab
Detailed description
This is a randomized, open-label, pilot study to evaluate the existence of a differential tumor immunomodulatory profile of neoadjuvant pembrolizumab in combination with paclitaxel and carboplatin vs pembrolizumab in combination with EC/AC in patients with triple negative, tumor infiltrating lymphocytes (TILs) enriched, early breast cancer to allow the optimization of future de-escalation strategies. There will be crossover between treatment arms when moving from the neoadjuvant to adjuvant treatment period for completion of standard chemotherapy plus pembrolizumab.
The chemotherapy regimen included in this study is built upon previous studies of pembrolizumab plus chemotherapy. The synergistic effect of different chemotherapy backbone and pembrolizumab will be studied as part of a 2-arm study:
Arm 1: (KXCb - PA[E]C): Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting.
Arm 2: (KPA[E]C - KXCb): Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting.
In case of clinical evidence of non-pCR, i.e., biopsy proven residual disease after the neoadjuvant phase, patients can proceed to the crossover part of the adjuvant phase before surgery (i.e., 4 cycles of chemotherapy plus pembrolizumab) receiving the remaining administrations of pembrolizumab after surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized
| Arm | Type | Receives |
|---|---|---|
| Arm 1: (KXCb - PA[E]C) | Active comparator | Drug: Pembrolizumab injectionPembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting. |
| (KPA[E]C - KXCb) | Experimental | Drug: Pembrolizumab injectionPembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (23 listed)
- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anticancer or anti-proliferative intent within the last 12 months.
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 |
|---|---|---|
| Pembrolizumab injectionAlso: Doxorubicin or Epirubicin, Cyclophosphamide, Paclitaxel, Carboplatin(KXCb - PA[E]C) vs (KPA[E]C - KXCb) Pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab in the adjuvant setting vs Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab in the adjuvant setting | Drug | (KPA[E]C - KXCb), Arm 1: (KXCb - PA[E]C) |
Primary outcome
Detect immunologic activation signal and the immunologically defined most suitable patient population for the synergistic interaction between pembrolizumab and chemotherapy backbone
Time frame: At the end of cycle 1 (each cycle is 28 days)
Compare signals of immunological activation or a more favorable immunological context beetween T cell subpopulations and transcriptional changes of T cell populations infiltrating tumors at baseline and C2D1
Rate of pCR
Time frame: 6 months to one year after subject inclusion
Compare the rate of pCR in subjects with locally advanced TNBC with TILs ≥ 10% in arm A and arm B at cycle 4
Primary translational endpoint
Time frame: 6 months to one year after subject inclusion
Quantification of number of T cells per mm2 with different phenotypes using fate bifurcation as defined as the proportion of TILs with the phenotype T-bet(hi) PD1(mid) CD8+.
2 secondary outcomes
Changes in the immunogenic phenotype
Time frame: 6 months to one year after subject inclusion
Incidence of treatment relatred Adverse events
Time frame: 6 months to one year after subject inclusion
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 17 Apr 2024.
- Individual participant dataSharing planned: Yes. Primary outcome will be shared in major medical Congress
Related trials for Early Breast Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingObservational study
Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
HR+/HER2- Early Breast Cancer
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
RecruitingObservational study
A Study to Assess Treatment Patterns and Treatment Adherence in Early HER2-positive Breast Cancer Participants After Treatment Decentralization
Early-stage HER2+ Breast Cancer
RecruitingPhase 2
Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Breast Neoplasms, Breast Cancer
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.
Fatima Cardoso, MD study director
Breast Unit Director
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab injection in people with Early Breast Cancer and Triple Negative Breast Cancer, run by Fundacao Champalimaud at 3 sites in Portugal.
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 0 inclusion and 23 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: opening soon, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Portugal. 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 Marcio Debiasi, MD (+351 210480048, marcio.debiasi@fundacaochampalimaud.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detect immunologic activation signal and the immunologically defined most suitable patient population for the synergistic interaction between pembrolizumab and chemotherapy backbone (time frame: At the end of cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Apr 2024.