Phase 1
Completed N=51
Japanese Phase 1 Trial of Sym004 in Solid Tumors
Source: ClinicalTrials.gov NCT01955473 ↗Enrolled (actual)
51
Serious AEs
21.6%
Results posted
Mar 2017
Primary outcomePrimary: Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A — 0; 0; 0; 0 subjects
Summary
This trial is to assess the safety and tolerability of Sym004, administered weekly or biweekly as monotherapy in Japanese subjects with advanced solid tumors.This study consisted of two parts, a dose-escalation part ("Part-A") and a dose-expansion part ("Part-B"). In Part-A, Sym004 will be administered weekly or biweekly as monotherapy in Japanese subjects with advanced solid tumors. In Part-B, Sym004 will be administered weekly as monotherapy to Japanese subjects with advanced esophageal squamous cell carcinoma (ESCC) as dose-expansion. A subject will receive Sym004 administration weekly at a dose that will determined to be the MTD or a dose that will lower than the MTD and determined to be appropriate with recommendation by Safety monitoring committee (SMC). The dose going to used in Part-B will be determined after safety confirmation of weekly regimens in Part-A of this trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With Dose Limiting Toxicities (DLTs) Determined in Part-A |
0; 0; 0; 0 | — |
| PRIMARY Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death |
3; 6; 6; 6; 30; 0 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose |
3685.5; 5893.1; 8957.3; 12783; 7073.5; 4109.0 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose |
NA; 7111.1; 15298; 13053; NA; 9738.5 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) at Week 1: Single Dose |
22.50; 23.24; 25.79; 21.69; 22.70; 25.09 | — |
| SECONDARY Dose Nornamized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 168 Hours (AUC0-168h) for the Weekly Regimen at Week 4: Multiple Dose |
NA; 43.90; 43.45; 42.38; NA; 59.12 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose |
17318; 22458 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose |
24755; 32336 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 1: Single Dose |
29.39; 38.11 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to 336 Hours (AUC0-336hours) For the Biweekly Regimen at Week 5: Multiple Dose |
42.45; 55.46 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 1: Single Dose |
19896; 27554 | — |
| SECONDARY Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose |
30127; 43308 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) at Week 1: Single Dose |
27.30; 30.33; 34.471; 33.77; 31.05; 31.86 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) for the Weekly Regimen at Week 4: Multiple Dose |
NA; 59.65; 77.86; 72.22; NA; 94.91 | — |
| SECONDARY Dose Normalized Area Under Concentration-time Curve (AUC) From Start of First Infusion to Infinity (AUC0-inf) For the Biweekly Regimen at Week 5: Multiple Dose |
51.67; 74.28 | — |
| SECONDARY Terminal Half-life (t1/2) of Sym004 at Week 1: Single Dose |
66.478; 79.041; 82.865; 111.69; 87.257; 74.075 | — |
| SECONDARY Terminal Half-life (t1/2) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
NA; 85.228; 135.98; 132.14; NA; 117.8 | — |
| SECONDARY Terminal Half-life (t1/2) of Sym004 For the Biweekly Regimen at Week 5: Multiple Dose |
130.39; 163.6 | — |
| SECONDARY Clearance (CL) of Sym004 at Week 1: Single Dose |
0.036626; 0.032967; 0.029012; 0.029615; 0.032202; 0.031385 | — |
| SECONDARY Clearance at Steady-state (CLss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
NA; 0.022778; 0.023015; 0.023589; NA; 0.017 | — |
| SECONDARY Clearance at Steady-state (CLss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose |
0.023552; 0.018 | — |
| SECONDARY Volume of Distribution at the Elimination Phase (Vz) of Sym004 at Week 1: Single Dose |
3.5130; 3.7593; 3.4688; 4.7726; 4.0536; 3.3543 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
NA; 2.7931; 4.4777; 4.4383; NA; 2.85 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose |
4.3988; 4.20 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose |
50.131; 85.088; 120.37; 157.71; 88.589; 54.660 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
76.094; 86.763; 181.62; 143.79; 89.26; 91.70 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose |
187.40; 224.0 | — |
| SECONDARY Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 at Week 1: Single Dose |
0.306; 0.336; 0.346; 0.268; 0.284; 0.334 | — |
| SECONDARY Dose Nornamized Maximum Serum Concentration (Cmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
0.486; 0.524; 0.516; 0.466; 0.570; 0.553 | — |
| SECONDARY Dose Normalized Maximum Serum Concentration (Cmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose |
0.318; 0.380 | — |
| SECONDARY Trough Concentrations (Ctrough) of Sym004 |
8.38333; 16.3617; 29.4483; 45.1117; 20.1517; 19.8700 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of Sym004 at Week 1: Single Dose |
2.07; 5.12; 5.73; 7.21; 6.30; 2.05 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of Sym004 for the Weekly Regimen at Week 4: Multiple Dose |
10.1; 5.94; 9.13; 5.13; 2.07; 6.13 | — |
| SECONDARY Time to Reach Maximum Concentration (Tmax) of Sym004 for the Biweekly Regimen at Week 5: Multiple Dose |
7.03; 5.28 | — |
| SECONDARY Percentage of Subjects With Best Overall Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Duration of Overall Response |
25.85; 10.40 | — |
| SECONDARY Percentage of Subjects With Disease Control |
66.7; 66.7; 50.0; 16.7; 56.7 | — |
| SECONDARY Duration of Disease Control |
6.10; 5.35; 24.60; 6.10; 5.90 | — |
| SECONDARY Time to Progression |
2.37; 2.33 | — |
| SECONDARY Progression-free Survival Time |
2.12; 2.30 | — |
| SECONDARY Anti-drug Antibody Titers |
— | — |
| SECONDARY Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression in Skin Tissues by Immunohistochemistry (IHC) |
0.0; 0.0; 0.0; 0.0; 7.7; 0.0 | — |
| SECONDARY Percentage of Participants With EGFR Amplification Using Fluorescent in Situ Hybridization (FISH) Method. |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
Eligibility Criteria
Inclusion Criteria
- Japanese male or female subjects aged greater than or equal to 20 years at the time of informed consent signature
- Histologically or cytologically confirmed cancer
- Refractory or recurrent advanced late stage solid tumors without available therapeutic options which are likely to provide patient benefit (failure and/or intolerance to standard anti-cancer therapy)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 3 months
- Written informed consent given before any trial-related activities are carried out
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Subjects with symptomatic brain metastases
- Subjects who received total resection or irradiation of the target lesion
- Received any of the following medications within 4 weeks before the first administration of Sym004 at Week 1: cytotoxic or cytostatic anti-cancer therapy, antibody therapy, tyrosine kinase inhibitors, and any investigational agent
- Received vaccine therapy as anticancer treatment within 12 weeks before the first administration of Sym004 at Week 1
- Diarrhea of greater than Grade 1 according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 (v4.03)
- Skin manifestation of greater than Grade 1 according to NCI-CTCAE (v4.03)
- Magnesium of less than 0.9 milligram per deciliter (mg/dL)
- Abnormal organ or bone marrow function as defined in the protocol
- Received immunosuppressive agents (including systemic corticosteroids used at doses above 20 milligram per day (mg/day) of prednisolone or equivalent) within 4 weeks before the first administration of Sym004 at Week 1
- Active severe infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the Investigator
- Known human immunodeficiency virus (HIV) positive, active Hepatitis B or C, or uncontrolled allergic conditions or allergy to Sym004 or its components
- Clinically significant cardiac disease or concurrent, uncontrolled medical condition
- Known previous Grade 3 to 4 infusion-related reactions, according to NCI-CTCAE (v4.03), with chimeric monoclonal antibodies
- Other protocol defined exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT01955473). 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.