Antineoplastic Agents

All Drugs and Chemicals

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Dose escalation will be conducted to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 . The dose may be escalated to the overseas recommended phase III dose.

Dose escalation with GSK2118436 may proceed until the overseas recommended phase III dose.

GSK2118436

GSK Clinical Trials

BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule.

BRF116056 is the first clinical experience with GSK2118436, a BRAF inhibitor, in Japan. This study will be designed to assess safety, tolerability, single and repeat dose PK profile and preliminary efficacy of GSK2118436 in Japanese subjects with BRAF V600 mutation positive solid tumors using continuous daily dosing schedule. Dose escalation of GSK2118436 will be performed according to a standard 3+3 dose-escalation design. GSK2118436 is given twice a day. However, to characterize the PK of GSK2118436 and its metabolites after single-dose administration, GSK2118436 will NOT be administrated for a week after the first administration. GSK2118436 continuous dosing will start after the 168-hour PK sample is obtained. Subjects may receive study treatment until disease progression, death or an unacceptable adverse event.

A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors

An Open-label, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of GSK2118436 in Japanese Subjects With BRAF V600 Mutation Positive Solid Tumors

Adverse Events will be graded by the investigator according to the NCI-CTCAE (version 4.0)

GlaxoSmithKline

Pharmaceutical Solutions

Gemcitabine

Carboplatin

Iniparib

Antimetabolites

Poly(ADP-ribose) Polymerase Inhibitors

* single cohort: SAR240550
* combination cohort: SAR240550 in combination with Gemcitabine and Carboplatin

Pharmaceutical form:sterile aqueous solution

Route of administration: intravenous

Iniparib (SAR240550 - BSI-201)

Clinical Sciences & Operations

Primary Objective:

- To determine a dose of SAR240550 to be further studied in combination with chemotherapy regimens

Secondary Objectives:

* To determine the dose limiting toxicity (DLT) of SAR240550 and SAR240550 in combination with chemotherapy regimen (gemcitabine and carboplatin
* To assess safety profiles: significant laboratory changes and adverse events (AEs)
* To make a preliminary assessment of antitumor effect in study subjects per Response Evaluation Criteria in Solid Tumors (RECIST) with measurable disease
* To characterize SAR240550 and metabolites, 4-iodo-3-amino benzamide (IABM) and 4-iodo-3-amino-benzoic acid (IABA), pharmacokinetics
* To collect blood samples for glutathione S-transferase (GST) genotypes at baseline)

Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

The duration of the study for each patient will include an up to 4-week screening phase, 21-day study cycle(s), followed by a 30 day follow-up.

Safety and Pharmacokinetics of SAR240550 (BSI-201) Twice Weekly in Patients With Advanced Solid Tumors

A Phase I Study Evaluating the Safety and Pharmacokinetics of SAR240550 Administered Twice Weekly in Patients With Advanced Solid Tumors.

Sanofi

Angiogenesis Inhibitors

AMG 780 will be administered by IV infusion every 2 weeks

AMG 780

This is a first in human, open-label, sequential dose escalation and expansion study of AMG 780 in up to 62 subjects with advanced solid tumors. The dose escalation part of the study is aimed at evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of AMG 780. The dose expansion will consist of up to 20 subjects and the dose level of AMG 780 will be dependent upon emerging safety and PK data from the dose escalation part of the study.

A Phase 1 Dose Escalation Study of AMG 780 in Adult Subjects With Advanced Solid Tumors

A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 780 in Adult Subjects With Advanced Solid Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of of GSK2118436 in Japanese Subjects With BRAF Mutation Positive Solid Tumors	NCT01582997	Cancer	GSK2118436	20 Years -	GlaxoSmithKline
Safety and Pharmacokinetics of SAR240550 (BSI-201) Twice Weekly in Patients With Advanced Solid Tumors	NCT01213381	Advance Solid T...	Iniparib (SAR24... Gemcitabine Carboplatin	20 Years -	Sanofi
A Phase 1 Dose Escalation Study of AMG 780 in Adult Subjects With Advanced Solid Tumors	NCT01137552	Advanced Solid ...	AMG 780	18 Years -	Amgen
Safety and Pharmacokinetics of SAR240550 (BSI-201) Twice Weekly in Patients With Advanced Solid Tumors	NCT01213381	Advance Solid T...	Iniparib (SAR24... Gemcitabine Carboplatin	20 Years -	Sanofi

Spots Global Cancer Trial Database for advance solid tumors