Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma

Brief summary public domain (ClinicalTrials.gov)

The main purpose of this first human study with CC-223 is to assess the safety and action of a new class of experimental drug (dual mTOR inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor type for later-stage clinical trials.

Detailed description public domain (ClinicalTrials.gov)

Initially, patients will be treated with oral CC-223 for one month. During this time, various tests (involving blood and urine collections, ECGs, etc) will be performed. Those whose tumors stabilize or regress may continue receiving treatment for as long as they benefit from CC-223. Different dose levels of CC-223 will be tested in a dose-rising study design.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Part A: Number of Participants With Dose-limiting Toxicities [From first dose up to 30 days after first dose]. Count Of Participants, Participants. Part A: CC-223 7.5 mg (n=1): 0; Part A: CC-223 15 mg (n=2): 0; Part A: CC-223 30 mg (n=9): 1; Part A: CC-223 45 mg (n=9): 1; Part A: CC-223 60 mg (n=7): 2.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Maximum Observed Plasma Concentration (Cmax) of CC-223 [Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, ng/mL (Geometric Coefficient of Variation). Day -1: Part A: CC-223 7.5 mg (n=1): 45.8 (NA) [Coefficient of Variation not calculable because data were only collected for 1 participant.]; Part A: CC-223 15 mg (n=2): 97.4 (57.5); Part A: CC-223 30 mg (n=8): 188 (41.8); Part A: CC-223 45 mg (n=9): 269 (65.7); Part A: CC-223 60 mg (n=7): 319 (70.0). Day 15: Part A: CC-223 7.5 mg (n=1): 50.8 (NA) [Coefficient of Variation not calculable because data were only collected for 1 participant.]; Part A: CC-223 15 mg (n=2): 92.0 (162.6); Part A: CC-223 30 mg (n=8): 293 (38.8); Part A: CC-223 45 mg (n=9): 417 (61.6); Part A: CC-223 60 mg (n=7): 480 (88.9).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Time to Maximum Concentration (Tmax) of CC-223 [Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Median, Hours (Full Range). Day -1/1: Part A: CC-223 7.5 mg (n=1): 1.00 (1.00 to 1.00); Part A: CC-223 15 mg (n=2): 1.25 (1.00 to 1.50); Part A: CC-223 30 mg (n=8): 1.55 (1.00 to 3.20); Part A: CC-223 45 mg (n=9): 3.00 (0.967 to 3.00); Part A: CC-223 60 mg (n=7): 1.50 (1.00 to 5.00). Day 15: Part A: CC-223 7.5 mg (n=1): 1.50 (1.50 to 1.50); Part A: CC-223 15 mg (n=2): 2.00 (1.00 to 3.00); Part A: CC-223 30 mg (n=8): 1.28 (0.500 to 3.03); Part A: CC-223 45 mg (n=9): 1.63 (0.500 to 8.00); Part A: CC-223 60 mg (n=7): 1.58 (1.00 to 3.00).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for CC-223 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, ng*h/mL (Geometric Coefficient of Variation). Day -1/Day 1: Part A: CC-223 7.5 mg (n=1): 318 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 347 (60.2); Part A: CC-223 30 mg (n=8): 1204 (37.8); Part A: CC-223 45 mg (n=9): 1493 (54.3); Part A: CC-223 60 mg (n=7): 2080 (100.8). Day 15: Part A: CC-223 7.5 mg (n=1): 179 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 282 (100.7); Part A: CC-223 30 mg (n=8): 1016 (39.2); Part A: CC-223 45 mg (n=9): 1351 (45.0); Part A: CC-223 60 mg (n=7): 1900 (93.5).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for CC-223 [0 to 24 hours post-dose on Day -1 and Day 15]. Geometric Mean, ng*h/mL (Geometric Coefficient of Variation). Day -1: Part A: CC-223 7.5 mg (n=1): 319 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 379 (45.2); Part A: CC-223 30 mg (n=8): 1144 (36.5); Part A: CC-223 45 mg (n=9): 1497 (45.5); Part A: CC-223 60 mg (n=7): 2031 (96.3). Day 15: Part A: CC-223 7.5 mg (n=1): 299 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 383 (88.8); Part A: CC-223 30 mg (n=8): 1443 (41.4); Part A: CC-223 45 mg (n=9): 2082 (29.3); Part A: CC-223 60 mg (n=7): 2954 (106.2).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) For CC-223 [Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, ng*h/mL (Geometric Coefficient of Variation). Day -1/1: Part A: CC-223 7.5 mg (n=1): 353 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 378 (49.7); Part A: CC-223 30 mg (n=8): 1234 (38.9); Part A: CC-223 45 mg (n=8): 1694 (41.8); Part A: CC-223 60 mg (n=6): 2074 (111.4).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Part A: Terminal Elimination Phase Half-Life (T1/2) of CC-223 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose]. Geometric Mean, Hours (Geometric Coefficient of Variation). Part A: CC-223 7.5 mg (n=1): 7.68 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 3.35 (54.1); Part A: CC-223 30 mg (n=8): 5.57 (38.4); Part A: CC-223 45 mg (n=8): 4.86 (25.9); Part A: CC-223 60 mg (n=6): 5.64 (16.7).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Apparent Total Body Clearance (CL/F) of CC-223 [Cycle 1 Day 1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, L/h (Geometric Coefficient of Variation). Day -1/1: Part A: CC-223 7.5 mg (n=1): 21.2 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 39.7 (49.7); Part A: CC-223 30 mg (n=8): 24.3 (38.9); Part A: CC-223 45 mg (n=8): 26.6 (41.8); Part A: CC-223 60 mg (n=6): 28.9 (111.4). Day 15: Part A: CC-223 7.5 mg (n=1): 25.1 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 39.2 (88.8); Part A: CC-223 30 mg (n=8): 20.8 (41.4); Part A: CC-223 45 mg (n=8): 21.6 (29.3); Part A: CC-223 60 mg (n=6): 20.3 (106.2).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Apparent Volume of Distribution (Vz/F) of CC-223 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose]. Geometric Mean, L (Geometric Coefficient of Variation). Part A: CC-223 7.5 mg (n=1): 235 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 192 (3.70); Part A: CC-223 30 mg (n=8): 195 (36.7); Part A: CC-223 45 mg (n=8): 186 (27.1); Part A: CC-223 60 mg (n=6): 236 (107.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part A: Percent Change From Baseline in Levels of Phosphorylated Ribosomal Protein S6 (pS6RP) in Stimulated B Cells [Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change (Full Range). Day -1 3 hours post-dose: Part A: CC-223 15 mg (n=1): -19.4 (-19.4 to -19.4); Part A: CC-223 30 mg (n=6): -73.6 (-86.1 to -58.5); Part A: CC-223 45 mg (n=8): -79.8 (-87.5 to -34.7); Part A: CC-223 60 mg (n=7): -76.6 (-83.4 to -60.2). Day 15 1.5 hours post-dose: Part A: CC-223 15 mg (n=1): 174.0 (174.0 to 174.0); Part A: CC-223 30 mg (n=6): -59.0 (-77.5 to -41.3); Part A: CC-223 45 mg (n=8): -80.5 (-84.6 to -80.0); Part A: CC-223 60 mg (n=7): -69.3 (-86.2 to -61.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part A: Percent Change From Baseline in Levels of Phosphorylated Elongation I Initiation Binding Protein (p4E-BP1) in Stimulated T Cells [Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in p4E-BP1 (Full Range). Day -1 3 hours post-dose: Part A: CC-223 15 mg (n=1): -20.7 (-20.7 to -20.7); Part A: CC-223 30 mg (n=9): -44.0 (-65.1 to -28.7); Part A: CC-223 45 mg (n=8): -55.7 (-71.2 to -26.4); Part A: CC-223 60 mg (n=7): -44.3 (-63.7 to -1.0). Day 15 1.5 hours post-dose: Part A: CC-223 15 mg (n=1): -14.4 (-14.4 to -14.4); Part A: CC-223 30 mg (n=9): -61.1 (-92.8 to -44.5); Part A: CC-223 45 mg (n=8): -54.8 (-61.8 to -34.4); Part A: CC-223 60 mg (n=7): -46.4 (-69.8 to -26.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part A: Percent Change From Baseline in Levels of Phosphorylated Protein Kinase B (pAKT) in Stimulated Monocytes [Cycle 1 Day -1: 3 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in pAKT (Full Range). Day -1 3 hours post-dose: Part A: CC-223 15 mg (n=1): -26.9 (-26.9 to -26.9); Part A: CC-223 30 mg (n=9): -56.5 (-72.2 to -31.7); Part A: CC-223 45 mg (n=8): -59.7 (-74.6 to -23.0); Part A: CC-223 60 mg (n=7): -48.4 (-53.6 to -26.7). Day 15 1.5 hours post-dose: Part A: CC-223 15 mg (n=1): 58.3 (58.3 to 58.3); Part A: CC-223 30 mg (n=9): -70.5 (-81.1 to -39.6); Part A: CC-223 45 mg (n=8): -55.8 (-70.1 to -42.0); Part A: CC-223 60 mg (n=7): -45.7 (-56.5 to -31.6).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Percent Change From Baseline in p4E-BP1 in Monocytes by Tumor Cohort [Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in p4E-BP1 (Full Range). Day 1,1.5 hours post-dose - CD3+: Part B: Hepatocellular Carcinoma (HCC) (n=44): -23.5 (-100.0 to 157.1); Part B: Neuroendocrine Tumor (NET) (n=34): -50.0 (-93.6 to 114.3); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -61.6 (-100.0 to 19.8); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -63.3 (-93.8 to 122.5). Day 15, 1.5 hours post-dose - CD3+: Part B: Hepatocellular Carcinoma (HCC) (n=44): -38.9 (-100.0 to 445.8); Part B: Neuroendocrine Tumor (NET) (n=34): -51.8 (-98.9 to 105.0); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -58.7 (-100.0 to 42.1); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -58.4 (-100.0 to 79.3). Day 1,1.5 hours post-dose - CD14+: Part B: Glioblastoma Multiforme (GBM) (n=10): -28.7 (-28.7 to -28.7); Part B: Hepatocellular Carcinoma (HCC) (n=44): -17.3 (-87.0 to 66.6); Part B: Neuroendocrine Tumor (NET) (n=34): -11.7 (-85.3 to 46.3); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -44.5 (-85.1 to 438.9); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -49.4 (-68.4 to 31.7). Day 15, 1.5 hours post-dose - CD14+: Part B: Glioblastoma Multiforme (GBM) (n=10): -61.3 (-61.3 to -61.3); Part B: Hepatocellular Carcinoma (HCC) (n=44): -58.1 (-91.7 to 528.1); Part B: Neuroendocrine Tumor (NET) (n=34): -39.1 (-78.7 to 26.0); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -74.1 (-94.1 to 210.2); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -35.8 (-70.0 to 154.7). Day 1,1.5 hours post-dose - CD19+: Part B: Glioblastoma Multiforme (GBM) (n=10): -15.3 (-15.3 to -15.3); Part B: Hepatocellular Carcinoma (HCC) (n=44): -44.3 (-100.0 to 266.7); Part B: Neuroendocrine Tumor (NET) (n=34): -39.4 (-93.7 to 34.3); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -44.5 (-71.9 to -36.0); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -44.8 (-88.3 to 58.2). Day 15, 1.5 hours post-dose - CD19+: Part B: Glioblastoma Multiforme (GBM) (n=10): -0.3 (-0.3 to -0.3); Part B: Hepatocellular Carcinoma (HCC) (n=44): -48.0 (-91.0 to 844.4); Part B: Neuroendocrine Tumor (NET) (n=34): -51.1 (-86.1 to 18.1); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -27.3 (-32.7 to -5.0); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -12.0 (-77.2 to 229.7). Day 1,1.5 hours post-dose - CD91+: Part B: Glioblastoma Multiforme (GBM) (n=10): -39.4 (-69.2 to 20.1); Part B: Hepatocellular Carcinoma (HCC) (n=44): -20.0 (-58.1 to 8.3); Part B: Neuroendocrine Tumor (NET) (n=34): -49.4 (-63.7 to -13.2); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=15): -24.5 (-32.4 to -16.6); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=6): -43.0 (-43.0 to -43.0); Part B: Non-small Cell Lung Cancer (NSCLC) (n=18): -24.9 (-57.6 to 28.1); Part B: Multiple Myelo

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Percent Change From Baseline in p4E-BP1 in Monocytes in the HCC and NET Cohorts by Dose [Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in p4E-BP1 (Full Range). Day 1 1.5 hours post-dose - CD3+: HCC 30 mg (n=20): -28.3 (-100.0 to 127.6); HCC 45 mg (n=6): 20.0 (-69.1 to 157.1); NET 30 mg (n=21): -40.4 (-93.6 to 11.6); NET 45 mg (n=13): -70.6 (-90.0 to 114.3). Day 15 1.5 hours post-dose - CD3+: HCC 30 mg (n=20): -34.0 (-100.0 to 445.8); HCC 45 mg (n=6): -52.8 (-62.6 to 52.4); NET 30 mg (n=21): -39.7 (-95.7 to 33.8); NET 45 mg (n=13): -70.2 (-98.9 to 105.0). Day 1 1.5 hours post-dose - CD14+: HCC 30 mg (n=20): -22.1 (-87.0 to 28.9); HCC 45 mg (n=6): 7.0 (-50.6 to 66.6); NET 30 mg (n=21): -8.7 (-54.7 to 25.8); NET 45 mg (n=13): -36.6 (-85.3 to 46.3). Day 15 1.5 hours post-dose - CD14+: HCC 30 mg (n=20): -58.1 (-91.7 to 528.1); HCC 45 mg (n=6): -28.4 (-67.5 to 111.6); NET 30 mg (n=21): -25.6 (-78.7 to 26.0); NET 45 mg (n=13): -47.4 (-68.3 to 23.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Percent Change From Baseline in Levels of pAKT in Monocytes by Tumor Cohort [Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in pAKT (Full Range). Day 1 1.5 hours post-dose: Part B: Non-small Cell Lung Cancer (NSCLC) (n=16): -68.1 (-86.5 to 43.9); Part B: Glioblastoma Multiforme (GBM) (n=8): -28.0 (-73.0 to 130.1); Part B: Hepatocellular Carcinoma (HCC) (n=16): -55.5 (-86.2 to 27.1); Part B: Neuroendocrine Tumor (NET) (n=4): -70.3 (-83.7 to -51.2); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=2): -54.3 (-89.0 to -19.6); Part B: Multiple Myeloma (MM) (n=4): -78.8 (-86.2 to -27.1); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=1): -53.8 (-53.8 to -53.8). Day 15 1.5 hours post-dose: Part B: Non-small Cell Lung Cancer (NSCLC) (n=16): -76.1 (-93.0 to -27.5); Part B: Glioblastoma Multiforme (GBM) (n=8): -34.1 (-89.8 to 48.6); Part B: Hepatocellular Carcinoma (HCC) (n=16): -84.1 (-87.7 to -19.5); Part B: Neuroendocrine Tumor (NET) (n=4): -52.2 (-52.2 to -52.2); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=2): -88.6 (-88.6 to -88.6); Part B: Multiple Myeloma (MM) (n=4): -52.9 (-77.5 to -28.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Percent Change From Baseline in Levels of pAKT in Monocytes in the HCC and NET Cohorts by Dose [Cycle 1 Day 1: 1.5 hours post-dose and Day 15: 1.5 hours post-dose]. Median, Percent change in pAKT (Full Range). Day 1 1.5 hours post-dose: HCC 45mg (n=16): -55.5 (-86.2 to 27.1); NET 45mg (n=4): -70.3 (-83.7 to -51.2). Day 15 1.5 hours post-dose: HCC 45mg (n=16): -84.1 (-87.7 to -19.5); NET 45mg (n=4): -52.2 (-52.2 to -52.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Percent Change From Baseline in pS6RP Levels in Tumor Tissue by Tumor Type [Up to Cycle 1 Day 15 3 hours post dose]. Median, Percent change in pS6RP (Full Range). Part B: Non-small Cell Lung Cancer (NSCLC) (n=6): 22 (-37 to 66); Part B: Glioblastoma Multiforme (GBM) (n=1): -36 (-36 to -36); Part B: Hepatocellular Carcinoma (HCC) (n=3): -19 (-37 to 24); Part B: Neuroendocrine Tumor (NET) (n=1): -30 (-30 to -30); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=9): -21 (-43 to 12); Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=3): -15 (-17 to 6).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part A: Overall Response Rate [From first dose up to tumor response (approximately 11 months)]. Number, Percentage of participants (90% Confidence Interval). Part A: CC-223 7.5 mg (n=1): 0; Part A: CC-223 15 mg (n=2): 0 (NA to NA) [Lower and upper limit not calculated due to insufficient number of events]; Part A: CC-223 30 mg (n=9): 11.1 (0.6 to 42.9); Part A: CC-223 45 mg (n=9): 0 (NA to NA) [Lower and upper limit not calculated due to insufficient number of events]; Part A: CC-223 60 mg (n=7): 0 (NA to NA) [Lower and upper limit not calculated due to insufficient number of events].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Part B: Overall Response Rate [From first dose up to tumor response (approximately 36 months)]. Number, Percentage of participants (95% Confidence Interval). Part B: Non-small Cell Lung Cancer (NSCLC) (n=26): 3.8 (0.1 to 19.6); Part B: Glioblastoma Multiforme (GBM) (n=13): 0 (NA to NA) [Lower and upper limit not calculated due to insufficient number of events]; Part B: Hepatocellular Carcinoma (HCC) (n=53): 5.7 (1.2 to 15.7); Part B: Neuroendocrine Tumor (NET) (n=47): 6.4 (1.3 to 17.5); Part B: Diffuse Large B-cell Lymphoma (DLBCL) (n=28): 10.7 (2.3 to 28.2); Part B: Multiple Myeloma (MM) (n=14): 0 (NA to NA) [Lower and upper limit not calculated due to insufficient number of events]; Part B: Hormone Receptor Positive Breast Cancer (HRPBC) (n=17): 11.8 (1.5 to 36.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Maximum Observed Concentration (Cmax) of Metabolite M1 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, ng/mL (Geometric Coefficient of Variation). Day -1: Part A: CC-223 7.5 mg (n=1): 143 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 284 (64.6); Part A: CC-223 30 mg (n=8): 729 (40.3); Part A: CC-223 45 mg (n=9): 1002 (37.2); Part A: CC-223 60 mg (n=7): 1174 (86.0). Day 15: Part A: CC-223 7.5 mg (n=1): 363 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 357 (139.8); Part A: CC-223 30 mg (n=8): 1681 (34.5); Part A: CC-223 45 mg (n=9): 2061 (23.1); Part A: CC-223 60 mg (n=7): 1946 (78.9).

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Time to Maximum Concentration (Tmax) of Metabolite M1 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Median, Hours (Full Range). Day 1: Part A: CC-223 7.5 mg (n=1): 8.00 (8.00 to 8.00); Part A: CC-223 15 mg (n=2): 2.28 (1.50 to 3.05); Part A: CC-223 30 mg (n=8): 6.51 (1.50 to 8.00); Part A: CC-223 45 mg (n=9): 5.00 (1.60 to 8.00); Part A: CC-223 60 mg (n=7): 5.00 (1.67 to 8.00). Day 15: Part A: CC-223 7.5 mg (n=1): 1.50 (1.50 to 1.50); Part A: CC-223 15 mg (n=2): 3.25 (1.50 to 5.00); Part A: CC-223 30 mg (n=8): 1.58 (1.00 to 3.03); Part A: CC-223 45 mg (n=9): 1.71 (0.00 to 3.20); Part A: CC-223 60 mg (n=7): 3.00 (0.00 to 5.00).

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Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for Metabolite M1 [Cycle 1 Day -1: pre-dose, 0.5, 1, 1.5, 3, 5, 8, 24 and 48 hours post-dose and Day 15: pre-dose, 0.5, 1, 1.5, 3, 5, and 8 hours post-dose]. Geometric Mean, ng*h/mL (Geometric Coefficient of Variation). Day 1: Part A: CC-223 7.5 mg (n=1): 4583 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 3788 (121.2); Part A: CC-223 30 mg (n=8): 18964 (45.1); Part A: CC-223 45 mg (n=9): 19938 (30.1); Part A: CC-223 60 mg (n=7): 23702 (98.1). Day 15: Part A: CC-223 7.5 mg (n=1): 6401 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 4388 (133.8); Part A: CC-223 30 mg (n=8): 27389 (48.5); Part A: CC-223 45 mg (n=9): 30823 (38.3); Part A: CC-223 60 mg (n=7): 33070 (101.6).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for Metabolite M1 [0 to 24 hours post-dose on Day -1 and Day 15]. Geometric Mean, ng*h/mL (Geometric Coefficient of Variation). Day 1: Part A: CC-223 7.5 mg (n=1): 2712 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 3207 (82.5); Part A: CC-223 30 mg (n=8): 12328 (39.4); Part A: CC-223 45 mg (n=9): 14107 (26.9); Part A: CC-223 60 mg (n=7): 16926 (89.2). Day 15: Part A: CC-223 7.5 mg (n=1): 6401 (NA) [Insufficient data values to calculate coefficient of variation.]; Part A: CC-223 15 mg (n=2): 4388 (133.8); Part A: CC-223 30 mg (n=8): 27389 (48.5); Part A: CC-223 45 mg (n=9): 30823 (38.3); Part A: CC-223 60 mg (n=7): 33070 (101.6).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Part B: Progression Free Survival (PFS) Rate at 6 Months for GBM Participants [From first dose to 6 months]. Number, Percentage of participants (95% Confidence Interval). Part B: Glioblastoma Multiforme (GBM) (n=13): 0 (NA to NA) [Lower and upper limit not reached to insufficient number of events].