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Ridaforolimus + Dalotuzumab

Phase 2

Breast Cancer | Small molecule | Oncology |Merck & Company, Inc.|Last Updated: May 31, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedCONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment212
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01234857A Study of Ridaforolimus (MK-8669) in Combination With Dalotuzumab (MK-0646) Compared to Standard of Care Treatment in Estrogen Receptor Positive Breast Cancer Patients (MK-8669-041 AM3)PHASE2 COMPLETED 115Sep 17, 2010Oct 15, 2013May 31, 2017 -
NCT00736970Oral Deforolimus With Trastuzumab for Patients With HER2-positive Trastuzumab-Refractory Metastatic Breast Cancer (8669-009)PHASE2 COMPLETED 34Jul 1, 2008May 1, 2011Aug 27, 2015 -
NCT01220570The Growth Factor Signature (GFS) as an Intermediate Biomarker of Response for Development of PI3K-Pathway Inhibitors in Patients With Breast Cancer (MK-8669-050)PHASE1 COMPLETED 63Sep 1, 2010Dec 1, 2012Jan 21, 2015 -
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Study Endpoints
Primary Endpoints
Progression free survival (PFS)
Assessed every 8 weeks until documentation of disease progression or death.

Progression free survival is defined as the time from randomization to progressive disease or death, which ever occurs earlier.

Objective Response Rate (ORR) measured by modified RECIST guidelines
Duration of the study
The population mean change from baseline in GFS (Growth Factor Signature) score
Baseline and Day 15
Secondary Endpoints
Objective response rate (ORR)
Assessed every 8 weeks until documentation of disease progression or death.
Overall survival (OS)
Every 3 months after participants go off active treatment
Characterize the overall safety and tolerability of oral deforolimus administered in combination with standard dose trastuzumab
Duration of the study
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Part A: ridaforolimus + dalotuzumabEXPERIMENTALApproximately 15 patients will be enrolled to the ridaforolimus-dalotuzumab combination treatment arm. Subsequent Patients are randomly assigned in a 1:1 ratio to treatment with the ridaforolimus (20 mg daily five days a week)/dalotuzumab (intravenous infusion 10 mg/kg once weekly) combination therapy or cross-over to exemestane single-therapy treatment.
Part A: exemestaneACTIVE_COMPARATORExemestane 25 mg daily; single-agent therapy.
Part B: ridaforolimus + dalotuzumabEXPERIMENTALPatients are randomly assigned in a 1:1 ratio to treatment with the ridaforolimus (20 mg daily five days a week)/dalotuzumab (intravenous infusion 10 mg/kg once weekly) combination therapy or cross-over to one of two single-therapy treatments (ridaforolimus alone or dalotuzumab alone). With the implementation of Amendment 3, this study arm will not be opened.
Part B: ridaforolimusEXPERIMENTALRidaforolimus; 40 mg daily five days a week, single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.
Part B: dalotuzumabEXPERIMENTALDalotuzumab intravenous infusion 10 mg/kg weekly; single-agent therapy. With the implementation of Amendment 3, this study arm will not be opened.
1EXPERIMENTAL10 mg oral tablets administered at 40 mg once daily for 5 consecutive days each week, followed by 2 days without ridaforolimus
Ridaforolimus + DalotuzumabEXPERIMENTALRidaforolimus (MK-8669) + Dalotuzumab (MK-0646)
RidaforolimusEXPERIMENTALRidaforolimus (MK-8669)
DalotuzumabEXPERIMENTALDalotuzumab (MK-0646)
Interventions
NameTypeDescription
ridaforolimus + dalotuzumabDRUGRidaforolimus 20 mg once daily (QD) five days a week, with the possibility of escalation to 30 mg once daily (QD) after the first cycle and dalotuzumab intravenous infusion 10 mg/kg once weekly (QW). Treatment will continue until disease progression.
exemestaneDRUGExemestane 25 mg daily (QD). Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval.
ridaforolimusDRUGRidaforolimus 40 mg QD five days a week. Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval. Note: the Sponsor-recommended dose of ridaforolimus when administered as a single agent is 40 mg/day, but when given in combination with dalotuzumab, it is given at 30 mg/day.
dalotuzumabDRUGDalotuzumab intravenous infusion 10 mg/kg QW. Treatment will continue until disease progression. Patients may cross-over to the combination therapy after disease progression at the discretion of the investigator with Sponsor approval.
trastuzumabDRUGsingle intravenous infusion every week; initial dose of 4 mg/kg over 90 minutes, then 2 mg/kg over 30 minutes
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Eligibility Criteria
Age Range18 Years — N/A
SexFEMALE
Healthy VolunteersNo

Inclusion Criteria The prospective participant must meet, at least, all of the criteria below to be eligible for study participation. The participant: * Has a confirmed diagnosis of breast cancer that is metastatic or locally advanced and is estrogen receptor positive and human epidermal growth fa...

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Competitive Landscape -Breast Cancer 408 trials
CompanyTickerTrialsLead PhaseDrugs
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib, Trastuzumab Deruxtecan, Paclitaxel, Trastuzumab
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy, Imlunestrant, Tamoxifen, Anastrozole
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1, Capecitabine, Paclitaxel, Nab-paclitaxel
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib, Alpelisib, Fulvestrant, Trastuzumab, Pertuzumab
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant, PF-07220060, letrozole, abemaciclib
BeOne Medicines Ltd. Sponsored ADRONC6PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib, Arm A: Gedatolisib + Palbociclib + Fulvestrant
Relay Therapeutics, Inc.RLAY2PHASE3RLY-2608, Capivasertib, Fulvestrant, Palbociclib, Ribociclib
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib, Pembrolizumab, Axatilimab
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam, Alisertib, Endocrine therapy
Immutep Ltd Sponsored ADRIMMP1PHASE2eftilagimod alpha, Paclitaxel
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