Phase 2
Completed N=226
Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma
Multiple Myeloma · Diffuse Large B-Cell Lymphoma · Glioblastoma multiforme · Hepatocellular Carcinoma
Source: ClinicalTrials.gov NCT01177397 ↗
Enrolled (actual)
226
Serious AEs
51.8%
Results posted
Nov 2022
Primary outcomePrimary: Part A: Number of Participants With Dose-limiting Toxicities — 0; 0; 1; 1 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Dose-limiting Toxicities |
0; 0; 1; 1; 2 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of CC-223 |
45.8; 97.4; 188; 269; 319; 50.8 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of CC-223 |
1.00; 1.25; 1.55; 3.00; 1.50; 1.50 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for CC-223 |
318; 347; 1204; 1493; 2080; 179 | — |
| PRIMARY Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for CC-223 |
319; 379; 1144; 1497; 2031; 299 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) For CC-223 |
353; 378; 1234; 1694; 2074 | — |
| PRIMARY Part A: Terminal Elimination Phase Half-Life (T1/2) of CC-223 |
7.68; 3.35; 5.57; 4.86; 5.64 | — |
| PRIMARY Apparent Total Body Clearance (CL/F) of CC-223 |
21.2; 39.7; 24.3; 26.6; 28.9; 25.1 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) of CC-223 |
235; 192; 195; 186; 236 | — |
| PRIMARY Part B: Progression Free Survival (PFS) Rate at 6 Months for GBM Participants |
— | — |
| SECONDARY Part A: Percent Change From Baseline in Levels of Phosphorylated Ribosomal Protein S6 (pS6RP) in Stimulated B Cells |
-19.4; -73.6; -79.8; -76.6; 174.0; -59.0 | — |
| SECONDARY Part A: Percent Change From Baseline in Levels of Phosphorylated Elongation I Initiation Binding Protein (p4E-BP1) in Stimulated T Cells |
-20.7; -44.0; -55.7; -44.3; -14.4; -61.1 | — |
| SECONDARY Part A: Percent Change From Baseline in Levels of Phosphorylated Protein Kinase B (pAKT) in Stimulated Monocytes |
-26.9; -56.5; -59.7; -48.4; 58.3; -70.5 | — |
| SECONDARY Part B: Percent Change From Baseline in p4E-BP1 in Monocytes by Tumor Cohort |
-23.5; -50.0; -61.6; -63.3; -38.9; -51.8 | — |
| SECONDARY Part B: Percent Change From Baseline in p4E-BP1 in Monocytes in the HCC and NET Cohorts by Dose |
-28.3; 20.0; -40.4; -70.6; -34.0; -52.8 | — |
| SECONDARY Part B: Percent Change From Baseline in Levels of pAKT in Monocytes by Tumor Cohort |
-68.1; -28.0; -55.5; -70.3; -54.3; -78.8 | — |
| SECONDARY Part B: Percent Change From Baseline in Levels of pAKT in Monocytes in the HCC and NET Cohorts by Dose |
-55.5; -70.3; -84.1; -52.2 | — |
| SECONDARY Part B: Percent Change From Baseline in pS6RP Levels in Tumor Tissue by Tumor Type |
22; -36; -19; -30; -21; -15 | — |
| SECONDARY Part A: Overall Response Rate |
0; 0; 11.1; 0; 0 | — |
| SECONDARY Part B: Overall Response Rate |
3.8; 0; 5.7; 6.4; 10.7; 0 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Metabolite M1 |
143; 284; 729; 1002; 1174; 363 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of Metabolite M1 |
8.00; 2.28; 6.51; 5.00; 5.00; 1.50 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) for Metabolite M1 |
4583; 3788; 18964; 19938; 23702; 6401 | — |
| SECONDARY Area Under the Concentration Time-Curve From 0-24 Hours After a Dose (AUC0-24) for Metabolite M1 |
2712; 3207; 12328; 14107; 16926; 6401 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically-confirmed advanced solid tumor, Non-Hodgkin Lymphoma or multiple myeloma
- Patients have not tolerated or progressed on standard therapy, and no further standard therapy is available
- Archival and screening tumor biopsy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (solid tumors), 0-2 (hematologic malignancy)
- Adequate organ function
Exclusion Criteria
- Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. Subjects must have recovered from any effects of recent radiotherapy that might confound the safety evaluation of study drug
- Symptomatic brain metastases (prior Rx and stable metastases are OK)
- Acute or chronic liver or renal disease or pancreatitis
- Diarrhea ≥ Grade 2, impaired GI absorption
- Impaired cardiac function
- Diabetes requiring Rx, glucose >126 mg/dL, HbA1c ≥6.5%
- Peripheral neuropathy ≥ Grade 2
- Pulmonary fibrosis
- Known HIV infection
- Known chronic hepatitis B or C virus (HBV/HCV) infection, unless comorbidity in subjects with HCC
- Pregnant, inadequate contraception
- Most concurrent second malignancies
Data sourced from ClinicalTrials.gov (NCT01177397). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.