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CP-751,871 + carboplatin + paclitaxel

Phase 1

Carcinoma, Non-Small-Cell Lung | Small molecule | Oncology |Pfizer, Inc.|Last Updated: Oct 30, 2013

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 Enrollment347
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00603538Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Advanced Lung CancerPHASE1 COMPLETED 19Jan 1, 2008May 1, 2009Apr 11, 20131 Japan
NCT00560573Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve Patients With Advanced Non-Small Cell Lung CancerPHASE1 COMPLETED 46Nov 1, 2007Mar 1, 2010Mar 21, 20134 Belgium, Ireland +1
NCT00147537Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung CancerPHASE1 COMPLETED 282Feb 1, 2005Aug 1, 2011Oct 30, 201331 United States, Canada +2
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Study Endpoints
Primary Endpoints
Number of Participants With Dose Limiting Toxicities (DLT)
Cycle 1

A DLT was defined as any one of the following adverse events observed in Cycle 1 which was considered as related to CP-751,871 combination therapy; 1) \>=Grade 3 gastrointestinal toxicity, hyperglycemia and/or fatigue despite the use of adequate/optimal medical intervention, 2) Any other \>=Grade 3 toxicity not classified under CTCAE blood/bone marrow, or 3) Grade 4 neutropenia that persisted for \>=7 consecutive days or was complicated by fever (defined as a body temperature \>38.0 Celsius degree), 4) Grade 3 thrombocytopenia which needed blood transfusion or Grade 4 thrombocytopenia.

Number of Participants With Dose-limiting Toxicities (DLT)
Start of treatment up to end of Cycle 1, Day 21

Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count \<500 cells/cubic millimeter \[mm\^3\]) \>=7 days, febrile neutropenia (Gr 3, fever \>=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet \<25,000 cells/mm\^3), Gr 3 thrombocytopenia \>=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment

Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b
Start of treatment (baseline) up to the end of Cycle 1 (Day 21)

The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity.

Recommended Phase 2 Dose (RP2D): Phase 1b
Start of treatment (baseline) up to the end of Cycle 1 (Day 21)
Objective Response Rate: Phase 2
Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2
Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Secondary Endpoints
Maximum Observed Concentration (Cmax) of CP-751,871
Cycles 1 and 4 at prior to dosing of CP-751,871 (Day 1), and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Plasma Decay Half-Life (t1/2)
Cycle 1 : prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Area Under the Plasma Concentration-time Curve From Time 0 to Day 22 (AUC0-day22)
Cycle 1: prior CP-751,871 (Day 1) to dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
CP-751,871EXPERIMENTAL -
1EXPERIMENTAL -
Phase 2 (Arms A & B)EXPERIMENTALCP-751,871 + paclitaxel + carboplatin
Phase 1bEXPERIMENTAL1. Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin 2. Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
Interventions
NameTypeDescription
CP-751,871 + carboplatin + paclitaxelDRUGChemotherapy (carboplatin and paclitaxel) and CP-751,871 (6, 10 or 20mg/kg) will be administered by intravenous infusion every three weeks.
CP-751,871DRUGCP-751,871 at doses ranging from 6 to 20 mg/Kg on Day 1 of each 21-day cycle. CP-751,871 may be administered even after active comparators discontinuation, for a total number of 17 cycles (1 year).
CisplatinDRUGCisplatin 75\* mg/m2 or 80\* mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycles. \* 75 mg/m2 when in combination with pemetrexed, 80 mg/m2 when in combination with gemcitabine
GemcitabineDRUGGemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles
PemetrexedDRUGPemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle
paclitaxelDRUGPhase 2 Arm A: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles Phase 2 Arm B: Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles
carboplatinDRUGPhase 2 Arm A: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles Phase 2 Arm B: Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles
erlotinibDRUGPhase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)
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Eligibility Criteria
Age Range20 Years — 74 Years
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Diagnosis of advanced non-small cell lung cancer * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: * Any prior treatment for non-small cell lung cancer * Brain metastases * With diabetes

Countries:JapanBelgiumIrelandSpainUnited StatesCanadaItaly
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