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

Sponsor

Helix BioPharma Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT02309892

Collaborator

Theradex (Industry)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: L-DOS47	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Aug 1, 2019

Actual Study Completion Date :

Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pemetrexed and Carboplatin plus L-DOS47 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.	Drug: L-DOS47 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.

Arm

Intervention/Treatment

Experimental: Pemetrexed and Carboplatin plus L-DOS47

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.

Drug: L-DOS47

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.

Outcome Measures

Primary Outcome Measures

Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin [Participants will be followed for 12 weeks]
The AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

Secondary Outcome Measures

Objective response rate of patients receiving the combination treatment according to RECIST 1.1 [Up to 12 weeks]
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.
Number of patient receiving a sustained clinical benefit [Up to 12 weeks]
Defined as the percentage of patients who have achieved complete response, partial response, and stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin.
Maximum observed plasma concentration (Cmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [Up to 12 weeks]
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Time to maximum observed plasma concentration (Tmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [Up to 12 weeks]
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Area under the concentration (AUC) vs time curve of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [Up to 12 weeks]
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
Terminal elimination half-life of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin [Up to 12 weeks]
Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47
The presence of anti-L-DOS47 antibodies for patients dosed with L-DOS47 in combination treatment with pemetrexed/carboplatin [Up to 12 weeks]
Serum samples will be collected and analyzed from all patients dosed with L-DOS47

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Main Inclusion Criteria:

Male or female patient ≥ 18 years of age
Histologically or cytologically confirmed non-squamous NSCLC
EGFR-mutation positive patients must have progressed on or had intolerance to an EGFR small molecule tyrosine kinase inhibitor
Patients whose tumors harbor an anaplastic lymphoma kinase (ALK) translocation must have progressed on or had intolerance to an ALK inhibitor;
No prior adjuvant chemotherapy within 1 year of the first treatment day if there is recurrent disease
At least 1 site of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and minimum life expectancy of ≥ 3 months
Adequate bone marrow, renal and liver function

Main Exclusion Criteria:

Histologic evidence of predominantly squamous cell NSCLC
Brain metastasis and/or leptomeningeal disease (known or suspected)
Peripheral neuropathy > CTCAE grade 1
Possibility of a curative local treatment (surgery and/or radiotherapy)
Previous chemotherapy except adjuvant treatment with progression of disease documented ≥ 12 months after end of adjuvant treatment
Having received treatment in another clinical study within the 30 days prior to commencing study treatment or having side effects of a prior study drug that are not recovered to grade ≤ 1 or baseline, except for alopecia
Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy