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 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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: L-DOS47

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States
      • University Hospitals Case Medical Center
  • Texas
    • Houston, Texas, United States
      • The University of Texas Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

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

Main Exclusion Criteria:

1. Histologic evidence of predominantly squamous cell NSCLC
2. Brain metastasis and/or leptomeningeal disease (known or suspected)
3. Peripheral neuropathy > CTCAE grade 1
4. Possibility of a curative local treatment (surgery and/or radiotherapy)
5. Previous chemotherapy except adjuvant treatment with progression of disease documented ≥ 12 months after end of adjuvant treatment
6. 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
7. Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Helix BioPharma Corporation
• Collaborators: Theradex

Publications and helpful links

Helpful Links

• Helix BioPharma corporate website

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: April 9, 2013
• First Submitted That Met QC Criteria: December 3, 2014
• First Posted (Estimate): December 5, 2014

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 20, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Neoplasms; Immunoconjugate; Tumor microenvironment alkalinization
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LDOS001