Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Recurrence

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Pemetrexed

Immunoconjugates

Patients will be recruited into cohorts of L DOS47 escalating doses, with a minimum of 3 and a maximum of 6 patients per cohort. The starting dose of L DOS47 will be 0.59 µg/kg; further possible dose levels that may be assessed are 0.78, 1.04, 1.38 and 1.84 µg/kg. The standard of care doses of pemetrexed \[500 mg/m2\] and carboplatin \[AUC6\], respectively, to be administered in combination with L-DOS47, will remain constant across cohorts.

A treatment cycle will be 21 days, with patients receiving L DOS47 on cycle Days 1, 8, and 15 and pemetrexed/carboplatin on Day 1 of each treatment cycle.

L-DOS47

The primary purpose of this research study is to evaluate how safe, how well tolerated and how effective a range of doses of L-DOS47 in combination with standard doublet therapy of pemetrexed/carboplatin in patients with Stage IV (TNM M1a and M1b) recurrent or metastatic non-squamous Non-Small Cell Lung Cancer.

It is planned that patients will receive 4 cycles of combination treatment with L-DOS47 + pemetrexed/carboplatin. Patients who have not progressed following the 4 cycles of combination treatment and who have not experienced unacceptable toxicity will have the opportunity to continue to receive L-DOS47 treatment for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression. Patients who are unable to complete 4 cycles of L-DOS47 + pemetrexed/carboplatin combination treatment due to pemetrexed/carboplatin toxicity will have the opportunity to continue receiving L-DOS47 treatment following discontinuation of pemetrexed/carboplatin, for as long as there is clinical benefit and it is well-tolerated, in the opinion of the Investigator, until disease progression.

A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC

A Phase I, Open Label, Dose Escalation Study of Immunoconjugate L-DOS47 in Combination With Pemetrexed/Carboplatin in Patients With Stage IV (TNM M1a and M1b) Recurrent or Metastatic NSCL Lung Cancer

The AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

Objective tumor response will be assessed according to RECIST version 1.1 in patients who have completed at least 2 cycles of study treatment and who have at least 1 post-treatment disease assessment.

Defined as the percentage of patients who have achieved complete response, partial response, and stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin.

Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47

Serum samples will be collected and analyzed from all patients dosed with L-DOS47

Theradex

Helix BioPharma Corporation

Patient will be recruited into cohorts of L-DOS47 escalating doses, with a minimum of 3 and a maximum of 6 patients per cohort. The starting dose of L-DOS47 will be 0.12 μg/kg; further possible dose levels include 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45, 3.26 and 4.33 μg/kg.

A treatment cycle will be 21 days with patients receiving L-DOS47 on cycle Days 1 and 8.

Dariusz Kowalski, MD, PhD

The primary purpose of this research study is to evaluate how safe, how well tolerated and how effective a range of doses of L-DOS47 in patients with non-squamous non-small cell lung cancer when given as a monotherapy.

Patients will be recruited into cohorts, with a minimum of three and a maximum of six patients per cohort. All patients at a given dose level must complete Cycle 1 (3 week period) before escalation in subsequent patients can proceed. The decision for dose escalation to the next dose level will be made after the safety and available pharmacokinetic (PK) data have been reviewed by the Trial Steering Committee (TSC).

Escalation of L-DOS47 will continue until a maximum tolerated dose (MTD) is reached.

After the MTD of L-DOS47 has been determined in Phase I, up to 20 patients will be enrolled (taken forward from Phase I) to evaluate the preliminary efficacy of L-DOS47 (i.e., response rate using the Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1 criteria, disease progression and survival); monitoring will include radiologic evaluations every second cycle. The safety and tolerability of L-DOS47 will also be further evaluated. Pharmacokinetic information will be collected as well as relevant observations on the activity of L-DOS47.

For all patients, treatment with L-DOS47 will continue either until the patient experiences disease progression, unacceptable toxicity, the patient withdraws consent or has completed four treatment cycles and does not wish to continue with additional cycles, whichever occurs first. After four cycles, patients may continue to receive L-DOS47 for as long as there is sustained clinical benefit and it is well tolerated, in the opinion of the Investigator.

A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47

A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients

Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patient dosed with L-DOS47.

Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

Assessed by the incidence and severity of AEs and SAEs and changes in vital signs

Safety parameters include clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG

Serum samples will be collected and analyzed from all patients dosed with L-DOS47.

Pharm-Olam International

Rare Diseases

Adenocarcinoma

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Adenocarcinoma

Pharmaceutical Solutions

Vinorelbine

Cisplatin

Tubulin Modulators

Antimitotic Agents

L-DOS47 (6/9/12 µg/kg) is administered by iv on Day 1 and 8 of each 21-day treatment cycle, in combination with iv administration of standard cisplatin (80 mg/m2) on Day 2 + vinorelbine (30 mg/m2) on Day 2 and 9.

Administration by iv of standard Cisplatin (80 mg/m2) on Day 1 + vinorelbine (30 mg/m2) on Day 1 and 8 of each 21-day treatment cycle.

L-DOS47 lyophilized powder reconstituted and diluted for iv injection

Cisplatin concentrate for solution for iv infusion

Vinorelbine concentrate for solution for iv infusion

Cezary Szczylik, MD, Ph.D.

This study will determine the highest dose of L-DOS47 that can be given in combination with vinorelbine/cisplatin, evaluate safety and tolerability of L-DOS47 when given in combination with vinorelbine/cisplatin, and assess how effective this combination is in treating patients with lung adenocarcinoma compared to patients who are given vinorelbine/cisplatin alone.

The study is divided into two parts. In part I, the maximum tolerated dose of L-DOS47, when given in combination with vinorelbine/cisplatin, will be determined. Cohorts of 3 patients will be recruited into three dosing cohorts (6, 9 and 12 µg/kg). All patients at a given dose level must complete the first treatment cycle (3 week period) before escalation in subsequent patients can proceed. The decision for escalation to the next dose level will be made after the safety data have been reviewed by the Trial Steering Committee (TSC). If a patient in any cohort experiences a dose limiting toxicity, an additional 3 patients will be enrolled, for a maximum of up to 18 patients in this initial dose escalation part of the study.

In part II, after the maximum tolerated dose of L-DOS47 in combination with vinorelbine/cisplatin has been determined, a further 118 patients will be randomized (1:1) to receive L-DOS47 in combination with vinorelbine/cisplatin, or vinorelbine/cisplatin alone. Efficacy will be assessed by time to progression (time from first day of study drug administration to documented disease progression), response rate (proportion of patients with a best overall response of complete response and partial response using the Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1 criteria), and overall survival (time from first day of study drug administration to death due to any cause). Monitoring will include radiological evaluations every second cycle. Safety and tolerability of L-DOS47 in combination will also continue to be evaluated.

For all patients, treatment will continue either until the patient experiences disease progression, unacceptable toxicity, the patient withdraws consent or has completed four treatment cycles.

Part I includes a brief initial dose escalation phase, followed by Part II, which includes a randomized treatment phase.

A Study of L-DOS47 in Combination With Vinorelbine/Cisplatin in Lung Adenocarcinoma

A Phase II, Open-Label, Randomized Study Immunoconjugate L-DOS47 in Combination With Vinorelbine/Cisplatin Versus Vinorelbine/Cisplatin Alone in Patients With Lung Adenocarcinoma

Time from first day of study drug administration to documentation of disease progression (including death due to progression)

Proportion of patients with a best overall response of complete response and partial response

Time to death as defined as time from first day of study drug administration to death to to any cause

Frequency of treatment emergent adverse events in patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC	NCT02309892	Non-Small Cell ...	L-DOS47	18 Years -	Helix BioPharma Corporation
A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC	NCT02309892	Non-Small Cell ...	L-DOS47	18 Years -	Helix BioPharma Corporation
A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47	NCT02340208	Non-Small Cell ...	L-DOS47	18 Years -	Helix BioPharma Corporation
A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47	NCT02340208	Non-Small Cell ...	L-DOS47	18 Years -	Helix BioPharma Corporation
A Study of L-DOS47 in Combination With Vinorelbine/Cisplatin in Lung Adenocarcinoma	NCT03891173	Lung Adenocarci...	L-DOS47 Cisplatin Vinorelbine	18 Years -	Helix BioPharma Corporation

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