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

December 20, 2023 updated by: Helix BioPharma Corporation

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 for the first and last two dosing cohorts, and a minimum of 1 and a maximum of 2 patients for the middle three dosing cohorts. The starting dose of L-DOS47 will be 0.59 µg/kg; further planned dose levels to be assessed are 0.78, 1.5, 3.0, 6.0, 9.0 and 12.0 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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin
Time Frame: Up to 12 weeks
Beginning with the start of study treatment at Cycle 1 Day 1 up to the last study visit: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or, is a congenital anomaly/birth defect. Beginning with the AE reporting period at the start of study treatment at Cycle 1 Day 1 up to the last study visit;
Up to 12 weeks
Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin.
Time Frame: Up to 21 days

A DLT was defined as the occurrence of any of the following events (according to NCI CTCAE version 4.0) that are considered to be (possibly/probably/definitely) related to L-DOS47 and occurring within 21 days after commencing study treatment:

  • Haematological adverse events ≥ grade 4
  • Non-haematological adverse events ≥ grade 3
  • One instance each of any two unique grade 2 adverse events
Up to 21 days
Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin
Time Frame: 21 days
Defined as the highest dose level at which ≤ 1 of 6 patients experiences a dose limiting toxicity (DLT) as assessed during the first treatment cycle. If no DLT are reported, it is assumed that the maximum tolerated dose of L-DOS47 in combination with pemetrexed/carboplatin was not reached.
21 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1
Time Frame: 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; where complete response (CR) is the disappearance of all target lesions and partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Up to 12 weeks
Percentage of Patients Receiving a Sustained Clinical Benefit
Time Frame: Up to 12 weeks
Defined as the percentage of patients who have achieved complete response, partial response, or stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin; where complete response (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and stable disease (SD) is where neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD, at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study).
Up to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Helix BioPharma Corporation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Theradex

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 20, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 19, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 20, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 9, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 5, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LDOS001

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