Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ridaforolimus · 21 trials · 28 indications
PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
Progression free rate at 6 months is defined as the proportion of participants who are a complete response (CR, disappearance of all target lesions), partial response (PR, at least a 30% decrease in the sum of the longest diameter of target lesions) or stable disease (does not qualify for PR or progressive disease) at 6 months from the date of the first study drug administration.
Tlag is the time taken for ridaforolimus to appear in systemic circulation following oral administration. The median and full range (minimum, maximum) for Tlag after a single dose of ridafolorlimus are presented.
AUC0-∞ represents the total exposure to ridaforolimus and its average blood concentration multiplied by the total amount of time (extrapolated to infinity) that ridaforolimus was in the body. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric mean and back-transformed 95% confidence interval are presented for AUC0-∞.
AUC0-24hr represents the total exposure to ridaforolimus and its average blood concentration multiplied by the total amount of time (extrapolated to 24 hours) that ridaforolimus was in the body. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for AUC0-24hr.
Cmax is the peak blood plasma concentration following a dose of ridaforolimus. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for Cmax.
C24hr is the concentration of ridaforolimus in the blood 24 hours after a dose of ridaforolimus. The (geometric) mean was calculated based on the back-transformed least-squares mean and the 95% confidence interval was determined from a linear mixed-effect model, containing a fixed effect for day and a random effect for participant, performed on natural log-transformed values. The geometric means and back-transformed 95% confidence intervals after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented for C24hr.
Tmax is the time at which the Cmax of ridaforolimus is reached. The medians and ranges (minimum, maximum) for Tmax after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented.
t½ is the time that it takes for the concentration of ridaforolimus in the body to decrease by half. The (harmonic) means and 95% confidence intervals for t1/2 after a single dose of ridaforolimus and after multiple doses of ridaforolimus are presented.
The mean change from baseline (CFB) in QTcF at 0.5 hours post-dose was assessed. At baseline (pre-dose) and at 0.5 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 1 hour post-dose was assessed. At baseline (pre-dose) and at 1 hour post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 2 hours post-dose was assessed. At baseline (pre-dose) and at 2 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 3 hours post-dose was assessed. At baseline (pre-dose) and at 3 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 4 hours post-dose was assessed. At baseline (pre-dose) and at 4 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 6 hours post-dose was assessed. At baseline (pre-dose) and at 6 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 8 hours post-dose was assessed. At baseline (pre-dose) and at 8 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 10 hours post-dose was assessed. At baseline (pre-dose) and at 10 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
The mean change from baseline (CFB) in QTcF at 24 hours post-dose was assessed. At baseline (pre-dose) and at 24 hours post-dose, 5 replicate electrocardiograms (ECGs) were collected to reduce measurement variability. The 5 replicate QTcF values were averaged to calculate the QTcF value for each participant. Further, each participant served as their own control for the calculation of CFB in QTcF after placebo and ridaforolimus 100 mg dosing. Additionally, CFB in QTcF after single ridaforolimus 100 mg dosing for each participant was adjusted for the CFB in QTcF observed after placebo dosing.
| Arm | Type | Description |
|---|---|---|
| Ridaforolimus | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Ridaforolimus + Dalotuzumab + Exemestane | EXPERIMENTAL | Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity. |
| Ridaforolimus + Exemestane | ACTIVE_COMPARATOR | Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity. |
| Ridaforolimus 40 mg | EXPERIMENTAL | - |
| Open Label | EXPERIMENTAL | ridaforolimus (MK8669)+ bicalutamide |
| 1 | EXPERIMENTAL | 40 mg once daily oral tablets for 5 days followed by 2 days without ridaforolimus |
| 2 | ACTIVE_COMPARATOR | Investigator's choice of: oral medroxyprogesterone acetate tablets 200 mg daily or oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily) OR Chemotherapy - carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin or topotecan administered as a single agent or as a doublet, and will be administered at doses and schedules chosen by the investigator |
| Ridaforolimus 20 mg + MK-2206 90 mg | EXPERIMENTAL | - |
| Ridaforolimus 20 mg + MK-2206 135 mg | EXPERIMENTAL | - |
| Ridaforolimus 30 mg + MK-2206 90 mg | EXPERIMENTAL | - |
| Ridaforolimus 30 mg + MK-2206 135 mg | EXPERIMENTAL | - |
| Ridaforolimus 30 mg + MK-2206 200 mg | EXPERIMENTAL | - |
| Ridaforolimus 40 mg + MK-2206 135 mg | EXPERIMENTAL | - |
| Ridaforolimus 40 mg + MK-2206 200 mg | EXPERIMENTAL | - |
| Ridaforolimus 20 mg + MK-0752 1800 mg | EXPERIMENTAL | No longer recruiting as of 19 July 2012 |
| Ridaforolimus 30 mg + MK-0752 1800 mg | EXPERIMENTAL | No longer recruiting as of 19 July 2012 |
| Ridaforolimus 40 mg + MK-0752 1800 mg | EXPERIMENTAL | No longer recruiting as of 19 July 2012 |
| All Participants | EXPERIMENTAL | In Part 1, all participants received a single oral dose of 2 mg midazolam on Day -2. On Days 1-5, all participants received daily single oral doses of ridaforolimus 40 mg ( 4 x 10 mg tablets). On Day 5, all participants received a single oral dose of 2 mg midazolam coadministered with the dose of ridaforolimus. Participants had the option to continue into Part 2 of this study. |
| Patients with Moderate Hepatic Insufficiency | EXPERIMENTAL | Patients with moderate hepatic insufficiency (a score of 7 to 9 on the Child-Pugh's scale) received a single 10 mg dose of ridaforolimus. |
| Healthy Control Subjects | EXPERIMENTAL | Healthy control subjects were matched by race, age, gender, and body mass index (BMI) to the patients with moderate hepatic insufficiency. The healthy control subjects also received a single 10 mg dose of ridaforolimus. |
| Pt 1. Placebo/Ridaforolimus 100 mg; Pt 2. Ridaforolimus 40 mg | EXPERIMENTAL | \[Pt 1, Day 1\]: Participants received a single dose of placebo (10 oral tablets) on Day 1 of Part 1. \[Pt 1, Day 2\]: Following completion of Part 1 / Day 1, participants received a single dose of ridaforolimus 100 mg (10 x 10 mg oral tablets) on Day 2 of Part 1. Following completion of Part 1 / Day 2, participants entered a washout period of ≥5 days before the first dose Part 2. \[Pt 2\]: Following completion of Part 1, participants received ridaforolimus 40 mg (4 x 10 mg oral tablets) given once daily (QD) for 5 consecutive days followed by 2 days off-drug. |
| 3 | EXPERIMENTAL | 40mg QDx5/wk ridaforolimus plus 15mg/kg Q3wks bevacizumab for 3 weeks |
| Cohort 1: Ridaforolimus 6.25 mg | EXPERIMENTAL | - |
| Cohort 2: Ridaforolimus 12.5 mg | EXPERIMENTAL | - |
| Cohort 3: Ridaforolimus 25 mg | EXPERIMENTAL | - |
| Cohort 4: Ridaforolimus 50 mg | EXPERIMENTAL | - |
| Cohort 5: Ridaforolimus 100 mg | EXPERIMENTAL | - |
| Cohort 6: Ridaforolimus 75 mg | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| ridaforolimus | DRUG | Four 10 mg tablets taken by mouth for 5 days per week continuously |
| Placebo | DRUG | Four 10 mg tablets taken by mouth for 5 days per week continuously |
| Dalotuzumab | DRUG | Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle. |
| Exemestane | DRUG | Exemestane 25 mg tablet administered PO QD. |
| ridaforolimus (MK8669) | DRUG | Three 10 mg tablets administered daily for 5 consecutive days each week followed by 2 days without ridaforolimus and one 50 mg tablet of bicalutamide administered once daily for 7 days each week. Treatment will continue until disease progression. |
| Comparator: Placebo | DRUG | Three tablets of matching placebo to ridaforolimus administered daily for 5 consecutive days each week followed by 2 days without matching placebo and on 50 mg tablet of bicalutamide administered once daily for 7 days each week. Treatment will continue until disease progression. |
| open-label ridaforolimus (MK8669) | DRUG | Single dose of three 10 mg tablets ridaforolimus on Day 1, and 50 mg bicalutamide once daily starting on Day 2. On Day 8, patients will begin taking three 10 mg tablets of ridaforolimus daily for 5 consecutive days each week followed by 2 days without ridaforolimus and one 50 mg tablet of bicalutamide once daily for 7 days each week. Treatment will continue until disease progression. |
| medroxyprogesterone acetate tablets OR megestrol acetate | DRUG | oral medroxyprogesterone acetate tablets 200 mg daily OR oral megestrol acetate tablets 40 mg 4 times per day (160 mg daily) |
| chemotherapy | DRUG | Chemotherapy - carboplatin, paclitaxel, doxorubicin, pegylated liposomal doxorubicin or topotecan administered as a single agent or as a doublet, and will be administered at doses and schedules chosen by the investigator |
| MK-0752 | DRUG | 300 mg capsule, orally, 6 capsules per dose, once each week. |
| MK-2206 | DRUG | Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week. |
| Midazolam | DRUG | A single oral dose of midazolam 2 mg (1 mL of 2 mg/mL syrup) was given on Day -2 and Day 5. |
| Ridaforolimus 100 mg | DRUG | Part 1: A single oral dose of 100 mg ridaforolimus (10 x 10 mg tablets) was given on Day 2. |
| Ridaforolimus 40 mg | DRUG | Part 2 (optional): Ridaforolimus 40 mg (4 x 10 mg tablets) was received on a regimen of daily oral doses for 5 consecutive days followed by 2 days off-drug. |
| bevacizumab | DRUG | IV infusion |
| Doxorubicin | DRUG | administered at 60 mg/m2 intravenously every 3 weeks |
Inclusion Criteria: * Confirmed diagnosis of metastatic soft-tissue or bone sarcoma * Ongoing complete response, partial response, or stable disease (RECIST) after a minimum of 4 cycles (and maximum of 12 months) of any one first, second, or third line of prior cytotoxic chemotherapy for metastatic...
Ridaforolimus + dalotuzumab is an investigational combination being studied in oncology. It has been evaluated in clinical trials for solid tumors, advanced or relapsed/refractory advanced cancer, breast neoplasms, prostate cancer, and in healthy volunteers. The combination is not approved and remains in clinical development.
Ridaforolimus + dalotuzumab is being developed by Merck & Company, Inc., traded on the New York Stock Exchange under the ticker MRK. The company has sponsored clinical trials evaluating this combination in various cancer settings.
Ridaforolimus + dalotuzumab has been studied in Phase 1 and Phase 2 clinical trials. The Phase 1 trials are completed, and a Phase 2 trial in breast cancer is also completed. The combination is investigational and not approved for any indication.
Ridaforolimus + dalotuzumab has been studied in completed trials including NCT00060632, NCT00112372, NCT00288431, and NCT01605396. These trials evaluated the combination in advanced malignancies, cancer, sarcoma, and breast cancer, with a total enrollment of 711 participants across all studies.
Ridaforolimus + dalotuzumab is a combination of two drugs, ridaforolimus and dalotuzumab. It is distinct from ridaforolimus alone. A Phase 2 trial compared ridaforolimus plus exemestane against ridaforolimus, dalotuzumab, and exemestane in breast cancer participants.