Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

In part A, patients in all dose cohorts will continue weekly treatment with the assigned dose of Sym004 until disease progression.

In Part B, patients will continue weekly treatment with the tolerated dose of Sym004 until disease progression.

In Part C, patients will receive weekly doses of Sym004 at the dose level below 12 mg/kg i.e. 9 mg/kg until disease progression.

In Part D and E, patients will receive doses of Sym004 administered every 2 weeks at dose level 12 mg/kg and 18 mg/kg, respectively until disease progression.

In Part F, patients will receive a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.

Sym004

Josep Tabernero, MD, PhD

This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts.

Part A investigates the safety and pharmacokinetics (PK) of escalating weekly dosing of Sym004 in patients with recurrent advanced solid tumors.

Part B and C validates the safety, PK and efficacy of weekly dosing of Sym004 at the maximum tolerated dose (MTD) in a homogenous patient population with advanced metastatic colorectal cancer (mCRC) and wild-type Kirsten rat sarcoma (KRAS). Part B will be initiated when a safe dose has been established in Part A.

If MTD equals 12 mg/kg, then part C will explore the 9 mg/kg level.

Part D and E is to validate the safety, PK and efficacy when administered every 2 weeks at doses of 12 mg/kg and 18 mg/kg, respectively.

Part F is to validate safety, PK and efficacy when administered with a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.

Sym004 in Patients With Advanced Solid Tumors

An Open-label, Multi-center Phase I Dose Escalation Study to Investigate the Safety and Tolerability of Multiple Doses of Sym004 in Patients With Advanced Solid Tumors

The AEs were used as a primary endpoint. AEs were summarized using descriptive statistics and presented overall by system organ class and preferred term. The frequencies of AEs were presented including number and percentages of participants with events and the total number of events.

Best Overall Response (OR) on the Full Analysis Set (FAS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, based on central evaluation with confirmatory CT scan or MRI \[Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR): CR + PR\]. Baseline was defined as Visit 2 (pre-infusion). The outcome measure was measured from screening until PD.

Median Progression Free Survival (PFS) was defined as the time interval without PD from start of first infusion until death or documented PD (i.e. at least a 20% increase in the sum of diameters of target lesions) according to RECIST v1.1. Patients who died without confirmed PD were considered as progressed. Patients who died or showed PD more than 21 days after last treatment were censored (i.e. were considered alive without progression on Day 21 after last treatment). Patients without events were censored at date of last scan or 22 days after last treatment, whichever occurred first.

Median Overall Survival (OS) was defined as the time from start of first infusion until date of death from any cause. Patients alive at the time of the analysis or prematurely withdrawn from the trial (e.g. lost to follow-up or consent withdrawn) were censored for the OS analysis. In any case of censoring, the date of censoring was the last time point documenting survival status.

For Part A, the endpoint was not calculated. For Parts B, C and F, the endpoint was calculated for each patient following the first and fourth Sym004 infusions.

For Parts D and E, the endpoint was calculated for each patient following the first and third Sym004 infusions.

T½ was estimated using non-compartmental methods and actual time points.

Outcome Measure Time Frame:

Parts B, C and F (Weekly dosing): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) until 1 week post-infusion (168-hours) and at Visit 5 (4th dose from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 1 week post-infusion (168-hours).

Parts D, E (Dosing every second week): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) to end of 3rd dose (from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 2 weeks post-infusion (336 hours).

Symphogen A/S

Any non-serious signs or symptoms occurring between Visit 1 and start of treatment at Visit 2 were recorded as medical history. In the survival period after end of trial, only SAEs with fatal outcome and SAEs considered related to Sym004 by the Investigator were collected.

Dose escalation in patients with refractory or recurrent advanced solid tumors.

Sym004 - 0.4 mg/kg, 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, 12 mg/kg, weekly - i.v. infusions

Part A: Dose Escalation

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004 - 12 mg/kg, weekly - i.v. infusions

Part B: Dose Expansion Cohort

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004 - 9 mg/kg, weekly - i.v. infusions

Part C: Dose Expansion Cohort

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004 - 12 mg/kg, once every 2 weeks - i.v. infusions

Part D: Dose Expansion Cohort

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004 - 18 mg/kg, once every 2 weeks - i.v. infusions

Part E: Dose Expansion Cohort

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004 - 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions

Part F: Dose Expansion Cohort

Dose escalation in patients with refractory or recurrent advanced solid tumors.

Sym004: 0.4 mg/kg, 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, 12 mg/kg, weekly - i.v. infusions

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 12 mg/kg, weekly - i.v. infusions

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 9 mg/kg, weekly - i.v. infusions

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 12 mg/kg, once every 2 weeks - i.v. infusions

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 18 mg/kg, once every 2 weeks - i.v. infusions

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Belgium

United States

Spain

Region of Enrollment

Disease duration

Part A: Dose escalation in patients with refractory or recurrent advanced solid tumors.

Parts B, C, D, E and F: Dose expansion cohorts in patients wíth advanced anti-EGFR antibody refractory mCRC.

Chief Scientific Officer

Number of Participants With Adverse Events (AEs)

Stable Disease

Progressive Disease

Partial Response

Missing

Not Evaluable

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 9 mg/kg weekly - i.v. infusions

Data for Part A were presented only for the FAS. For Parts B to F, analyses and summaries were performed both for the FAS and for the per protocol population. The FAS was considered the primary analysis population.

Antitumor Activity

Progression Free Survival

Overall Survival

Antitumor Activity Endpoints - Time-to-event Endpoints

1st Dose

3rd Dose

4th Dose

Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.

Sym004: 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusion

For Part A, data could not be reported as the endpoint was not calculated and no pharmacokinetics (PK) analysis set was defined. For Parts B to F, a PK analysis set was used.

Terminal Half-Life (T½)

Dose expansion cohort in patients with advanced anti-epidermal growth factor receptor (anti-EGFR) antibody refractory metastatic colorectal cancer (mCRC).

Sym004: 12 mg/kg, weekly - i.v. infusions

Spots Global Cancer Trial Database for Sym004 in Patients With Advanced Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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