Phase II Lenvatinib and Pembrolizumab in Endocrine Resistant Breast Cancer With Letrozole
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age21-99
SponsorNational Cancer Centre, Singapore
About this trial
This is a phase II study testing the combination of Pembrolizumab with Lenvatinib, a multi-kinase inhibitor that has activity against vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR1-4), ret protooncogene (RET), platelet-derived growth factor receptor-alpha (PDGFR-alpha) and KIT (a stem cell factor receptor), and letrozole, a non-steroidal aromatase inhibitor, in advanced hormone receptor (HR) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) that has progressed on/after standard endocrine therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male/female participants who are at least 21 years of age on the day of signing informed consent, with histologically or cytologically confirmed diagnosis of metastatic or locally advanced carcinoma of the breast not amenable to treatment with curative intent, will be enrolled in this study.
Disease progression after treatment with at least 1 line of palliative endocrine therapy in the metastatic setting.
There is no limit to the number of lines of prior palliative endocrine therapy. (Prior aromatase inhibitor in the curative and/or palliative setting is allowed.)
Prior targeted therapy in the locally advanced (recurrent or progressed) or metastatic setting, such as CDK4/6 inhibitors, mTOR inhibitors, PI3K inhibitors, is allowed with no limit to the number of lines of targeted therapy (prior Lenvatinib is not allowed).
Disqualifiers
A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
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).
Has received prior Lenvatinib.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 times the half-life, whichever is shorter) prior to allocation. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
Trial design
Design model
Single group
Treatments tested in this trial
Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole
DrugLenvatinib and Letrozole will be given orally (PO) daily from Day -14, while Pembrolizumab will be administered intravenously during week 1 of each 6-weekly cycle from Cycle 1 Day 1 (C1D1), with daily Lenvatinib and Letrozole.
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: InterventionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Objective Response Rate (ORR) per RECIST version 1.1
The efficacy of Pembrolizumab, Lenvatinib and Letrozole. ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR at the time of data cutoff, based on RECIST version 1.1.
Time frame
Up to 2 years.Secondary outcomes
1
Progression-Free Survival (PFS) per RECIST version 1.1
PFS is defined as the time from the first study dose date (at the D-14 Lenvatinib + Letrozole run-in phase) to the date of first documentation of confirmed disease progression or death (whichever occurs first) according to RECIST version 1.1.
Time frame
Up to 3 years after End of Treatment (estimated).2
Progression-Free Survival (PFS) per iRECIST
PFS is defined as the time from the first study dose date (at the D-14 Lenvatinib + Letrozole run-in phase) to the date of first documentation of confirmed disease progression or death (whichever occurs first) according to iRECIST criteria.
Time frame
Up to 3 years after End of Treatment (estimated).3
Objective Response Rate (ORR) per iRECIST
ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR at the time of data cutoff, based on iRECIST criteria.
Time frame
Up to 2 years.4
Duration of Response (DOR)
DOR is defined as the time from the date the criteria are met for an CR or PR (whichever is recorded first) to the date the disease progression is objectively documented. If a subject has no record of disease progression, then the subject's data will be censored at the last available tumour assessment.
Time frame
Up to 3 years after End of Treatment (estimated).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
National Cancer Centre, Singapore
Lead sponsor
MSD Pharma (Singapore) Pte Ltd
Collaborator
Source ClinicalTrials.gov