This study has been transitioned to CTIS with ID 2023-506752-24-00 check the CTIS register for the current data. 1) Objective: To compare pembrolizumab plus chemotherapy to placebo plus chemotherapy with respect to PFS
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To compare pembrolizumab plus chemotherapy to placebo plus chemotherapy with
respect to PFS
- To compare pembrolizumab plus chemotherapy to placebo plus chemotherapy with
respect to OS
Secondary outcome
- To compare pembrolizumab plus chemotherapy to placebo plus chemotherapy with
respect to ORR
- To compare pembrolizumab plus chemotherapy to placebo plus chemotherapy with
respect to DCR
- To evaluate DOR
- To evaluate the safety and tolerability of pembrolizumab plus chemotherapy.
Background summary
Breast cancer is the most frequently diagnosed malignancy and the leading cause
of cancer deaths in women worldwide. Respectively HR+/HER2- breast cancer
represents ~73% of all breast cancer cases. The 5-year OS rate for HR+/ HER2-
breast cancer is stage-dependent and ranges between 98% to 75% for Stages
I-III, respectively, whereas the 5-year OS rate in patients with distant
metastasis is no more than 30%.Once endocrine therapy resistance occurs, as it
does in all cases, sequential chemotherapy becomes the mainstay of current
treatment for HR+/HER2- MBC, where PFS and OS remain poor.
Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high
specificity of binding to the programmed cell death 1 (PD-1) receptor, thus
inhibiting its interaction with ligand PD-L1 and ligand PD-L2. Based on
preclinical in vitro data, pembrolizumab has high affinity and potent receptor
blocking activity for PD-1. Pembrolizumab has an acceptable preclinical safety
profile and is in clinical development as an intravenous (IV) immunotherapy for
advanced malignancies. Keytruda® (pembrolizumab) is indicated for the treatment
of patients across a number of indications.
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to
suppress immune control. The normal function of PD-1, expressed on the cell
surface of activated T- cells under healthy conditions, is to down-modulate
unwanted or excessive immune responses, including autoimmune reactions. As a
consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic
intervention of HR+/HER2- MBC.
Study objective
This study has been transitioned to CTIS with ID 2023-506752-24-00 check the CTIS register for the current data.
1) Objective: To compare pembrolizumab plus chemotherapy to placebo plus
chemotherapy with respect to PFS
Study design
This is a randomized, double-blind, placebo-controlled, Phase 3 Study of
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for the
treatment of chemotherapy-candidate Hormone Receptor-Positive, Human Epidermal
Growth Factor Receptor 2-Negative (HR+/HER2-) Locally Recurrent Inoperable or
Metastatic Breast Cancer.
Approximately 800 participants will be randomly assigned (with about 400
participants with CPS >=10) to two subgroups. After a screening
phase of up to 28 days, each participant will be randomly assigned to receive
study intervention until one of the conditions for discontinuation of
study intervention is met.
Participants who complete study intervention after receiving 35 administrations
of pembrolizumab, and participants who attain a complete
response and stop study intervention may be eligible for the Second Course and
receive up to 17 additional administrations of pembrolizumab
(approximately 1 year) upon experiencing disease progression.
At the end of treatment, each participant will be followed for the occurrence
of AEs and spontaneously reported pregnancy.
Participants who discontinue for reasons other than radiographic disease
progression will have posttreatment follow-up imaging for disease status
until any of the conditions for discontinuation of imaging are met.
All participants will be followed for overall survival until death, withdrawal
of consent, or the end of the study.
Intervention
Twee intervention groups
Drug: Dose Strength: Dose
Frequency: Admin: Treatment period: Use:
Arm 1: Pembrolizumab 200 mg Day
1 IV Every 21 days
Experimental
Paclitaxel 90 mg/m2 Day 1, day
8, day 15 IV Every 28 days Background Treatment
Nab-Paclitaxel 100 mg/m2 Day 1, day 8,
day 15 IV Every 28 days Background Treatment
Liposomaal doxorubicine 50 mg/m2 Day
1 IV Every 28 days Background
Treatment
Capecitabine 1000 mg/m2 BID days
1-14 PO Every 21 days Background
Treatment
Arm 2: Normal saline or dextrose N/A
N/A IV Every 21
days Placebo
Paclitaxel 90 mg/m2 Day 1, day 8, day
15 IV Every 28 days Background Treatment
Nab-Paclitaxel 100 mg/m2 Day 1, day 8, day
15 IV Every 28 days Background Treatment
Liposomaal doxorubicine 50 mg/m2 Day
1 IV Every 28 days Background
Treatment
Capecitabine 1000 mg/m2 BID days
1-14 PO Every 21 days Background
Treatment
Abbreviations: Admin = administration; BID = twice daily; IV = intravenously;
PO = orally.
Study burden and risks
For this study, patients will be subjected to invasive procedures such as blood
collection, Biopsy, CT-MRI or bone scans, physical exams, possibly
confrontational questionnaires, and patients will be asked to visit the
hospital regularly. Patients will be administered with different kinds of
medication (Pembro + Chemo OR Placebo + Chemo), during three-week cycles up to
a maximum of 35 treatments.
It cannot be guaranteed that participants in clinical studies will directly
benefit from study intervention during participation, as clinical studies are
designed to provide information about the safety and effectiveness of an
investigational medicine. Pembrolizumab has been administered in a large number
of cancer participants with a well characterized safety profile and has
received regulatory approval for multiple malignancies. Overall, pembrolizumab
is well tolerated at doses up to 10 mg/kg every 2 weeks (Q2W). Pembrolizumab
has also demonstrated anticancer clinical activity and efficacy in a broad
range of cancer indications.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
The main inclusion criteria are listed here. For a complete list of inclusion
please refer to the research protocol.
1. Has locally recurrent inoperable or metastatic HR+/HER2- breast cancer,
which has not been previously treated with cytotoxic chemotherapy in the
noncurative setting.
2. Has progressed on prior endocrine therapy and is now a chemotherapy
candidate, meeting the characteristics in regard to previous treatments of one
of the 4 groups.
3. Has presented a documented radiographic disease progression
4. Is a chemotherapy candidate that meets the criteria as described in the
protocol.
5. Provides a new or the last obtained core biopsy.
6. Has centrally confirmed PD-L1 CPS >=1 and HR+ (ER and/or PgR) /HER2- breast
cancer as defined by the most recent ASCO/CAP guidelines on most recent tumor
biopsy.
7. Has an ECOG Performance Status of 0 or 1, as assessed within 7 days prior to
the first dose of study treatment.
8. Demonstrates adequate organ function, within 10 days prior to the start of
study treatment, as defined in the protocol.
9. Participants are at least 18 years of age on the day of signing informed
consent
10. Male participants are eligible to participate if they agree to the criteria
as defined in the protocol during the study intervention period and for at
least 6 months after the last dose of chemotherapy.
11. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least 1 of the conditions defined in the protocol.
12. The participant (or legally acceptable representative if applicable)
provides documented informed consent for the study.
Exclusion criteria
The main exclusion criteria are listed here. For a complete list of exclusion
please refer to the research protocol.
1. Has breast cancer amenable to treatment with curative intent.
2. Has a history or current evidence of any condition, therapy, or laboratory
abnormality as defined in the protocol.
3. Has significant cardiac disease as defined in the protocol
4. Has advanced/metastatic, symptomatic visceral spread at risk of rapidly
evolving into life-threatening complications, see more information in the study
protocol.
5. Has skin only disease. Participants who have metastatic disease fulfilling
the previous criteria in addition to skin disease can be enrolled.
6. Has a known germline BRCA mutation and has not received previous treatment
with PARP inhibition either in the adjuvant or metastatic setting. Single-agent
PARP inhibitor therapy does not count as a line of endocrine therapy.
7. Has received prior chemotherapy for locally recurrent inoperable or
metastatic breast cancer.
8. 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 coinhibitory T-cell
receptor (eg, CTLA-4, OX-40, CD137).
9. Has received prior systemic anticancer therapy with other investigational
agents within 4 weeks prior to randomization.
10. Has received prior radiotherapy within 2 weeks of start of study
intervention or radiation-related toxicities requiring corticosteroids.
11. Has received a live or live attenuated vaccine within 30 days prior to the
first dose of study intervention.
12. Has received an investigational agent or has used an investigational device
within 4 weeks prior to study intervention administration.
13. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy or any other form of immunosuppressive therapy as defined in
the protocol.
14. Has a known additional malignancy that is progressing or has required
active treatment within the past 3 years.
15. Has known active CNS metastases as defined in the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506752-24-00 |
| EudraCT | EUCTR2020-005407-38-NL |
| CCMO | NL76778.056.21 |