Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AZD2014, Paclitaxel
AZD2014 3 on/4 off & weekly paclitaxel · 7 trials · 6 indications
To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) improves progression-free survival as compared to standard maintenance therapy in patients with metastatic Breast Cancer
The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.
The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.
The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
The mean cumulative percentage of \[14C\]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Mean AZD2014 Cmax values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
AZD2014 Tmax values for plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
AZD2014 t(last) values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Mean AUC for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 is presented.
Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 are presented.
The mean CL/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
The MRT of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
The mean Vss/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
The mean lambda\_z of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
The mean t1/2(lambda\_z) for AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Mean \[14C\] radioactivity Cmax values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
\[14C\] radioactivity tmax in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 is presented .
Mean \[14C\] radioactivity t(last) values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.
The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Mean fe%(R) values per urine collection period are presented as a percentage of the total \[14C\]-AZD2014 dose administered on Day 1.
CL(R) of AZD2014 from plasma up to 168 h post-dose.
fe cum%(R) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
fe cum%(f) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Safety and tolerability assessed through the incidence of adverse events.
This will be assessed in terms of Adverse Events (AEs), laboratory data, vital signs, ECG and physical exams
To determine the dose at which no more than one patient out of up to 6 patients at the same dose level experience a drug-related dose-limiting toxicity.
Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in \>1 patient
| Arm | Type | Description |
|---|---|---|
| Substudy 1: targeted agent | EXPERIMENTAL | Arm A1 / Targeted Arm : targeted maintenance from a list of 8 targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, bicalutamide tablet per os 150 od, continuous dosing, olaparib tablet per os 300 mg bd, continuous dosing |
| Substudy 1: standard maintenance therapy | ACTIVE_COMPARATOR | Arm B1/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin or Liposomal Doxorubicine), Taxanes (Paclitaxel, Docetaxel), Cyclophosphamide, DNA Intercalators (Capecitabine, 5-FU, gemcitabine), Methotrexate, Vinca alkaloids (Vinorelbine, Vinblastine, Vincristine), Platinum based chemotherapies (Carboplatin, Cisplatin), Bevacizumab, Mitomycin C, Eribulin |
| Substudy 2: Immunotherapy | EXPERIMENTAL | Arm A2/ Immunotherapy arm: maintenance with MEDI4736 for patient without actionable genomic alterations or non eligible to Targeted substudy 1, MEDI4736 Intra-venous 10 mg/kg, Q2W |
| Substudy 2: standard maintenance therapy | ACTIVE_COMPARATOR | Arm B2/ maintenance Standard Chemotherapy Arm : such as Anthracyclines (Doxorubicin or Epirubicin or Liposomal Doxorubicine), Taxanes (Paclitaxel, Docetaxel), Cyclophosphamide, DNA Intercalators (Capecitabine, 5-FU, gemcitabine), Methotrexate, Vinca alkaloids (Vinorelbine, Vinblastine, Vincristine), Platinum based chemotherapies (Carboplatin, Cisplatin), Bevacizumab, Mitomycin C, Eribulin |
| [14C]AZD2014 followed by AZD2014 Monotherapy | EXPERIMENTAL | Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 Monotherapy |
| [14C]AZD2014 followed by AZD2014 + Fulvestrant | EXPERIMENTAL | Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 + Fulvestrant |
| [14C]AZD2014 followed by AZD2014 + Paclitaxel | EXPERIMENTAL | Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 + Paclitaxel |
| Triplet Combination (Dose Finding) | EXPERIMENTAL | Phase 1 triplet dose finding phase in 3-6 patients per cohort - approximately 30 patients depending on emerging data to determine the maximum tolerated dose (MTD) of the triplet. |
| Triplet Combination (Dose Expansion) | EXPERIMENTAL | Additional patients will be enrolled at the dose determined in Part A. |
| AZD2014 50mg, 125mg, 25mg and 50mg intermittent BD | EXPERIMENTAL | 50mg BD continuous dosing, 125mg BD intermittent dosing, 25 mg and 50mg intermittent dosing with weekly Paclitaxel |
| AZD2014 3 on/4 off & weekly paclitaxel | EXPERIMENTAL | 3 days on, 4 days off AZD2014 BD administered orally Days 1-3 each week in combination with paclitaxel administered via IV infusion on Day 1 each week, in 7-week cycles (6 weeks treatment followed by 1 week rest). |
| AZD2014 2 on/5 off & weekly paclitaxel | EXPERIMENTAL | AZD2014 BD administered orally Days 1-2 each week in combination with paclitaxel administered via IV infusion on Day 1 each week, in 7-week cycles (6 weeks treatment followed by 1 week rest). |
| AZD2014 with Fulvestrant | EXPERIMENTAL | AZD2014 with Fulvestrant |
| AZD2014 | EXPERIMENTAL | AZD2014 dose escalation phase in Part A and expansion phase in Part B. |
| Name | Type | Description |
|---|---|---|
| AZD2014 | DRUG | Target: m-TOR |
| AZD4547 | DRUG | Target: EGFR |
| AZD5363 | DRUG | Target: AKT |
| AZD8931 | DRUG | Target: HER2, EGFR |
| Selumetinib | DRUG | Target: MEK |
| Vandetanib | DRUG | Target: VEGF, EGFR |
| Bicalutamide | DRUG | target: Androgen receptor |
| Olaparib | DRUG | Target: PARP |
| Anthracyclines | DRUG | DNA intercalation |
| Taxanes | DRUG | Target: mitotic tubulin and microtubules |
| cyclophosphamide | DRUG | Alkylating agents |
| DNA intercalators | DRUG | DNA intercalators |
| Methotrexate | DRUG | DNA intercalators |
| vinca alkaloids | DRUG | Target: mitotic tubulin and microtubules |
| Platinum based chemotherapies | DRUG | Platinum based chemotherapies |
| Bevacizumab | DRUG | Target: VEGF |
| Mitomycin C | DRUG | Alkylating agents |
| Eribulin | DRUG | Microtubule modulator |
| MEDI4736 | DRUG | Target: PD-L1 |
| [14C]AZD2014 | DRUG | Radiolabelled dual TORC1/TORC2 inhibitor |
| Multiple dose AZD2014 | DRUG | Dual TORC1/TORC2 inhibitor |
| Fulvestrant | DRUG | Hormonal Agent |
| Paclitaxel | DRUG | Taxane |
| Palbociclib | DRUG | cyclin dependent kinase inhibitor |
| AZD2014 3 on/4 off & weekly paclitaxel | DRUG | AZD2014 3 days on, 4 days off + weekly paclitaxel |
| AZD2014 2 on/5 off & weekly paclitaxel | DRUG | AZD2014 2 days on, 5 Days off + weekly paclitaxel |
Screening phase: Inclusion Criteria: * Women (or men) with histologically proven breast cancer * Metastatic relapse or progression or stage IV at diagnosis * No Her2 over-expression * Patients with metastases that can be biopsied, except bone metastases * Patients who are eligible for a first or a...
Top 2 of 3 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520/GEH200521 |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |