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

Phase 1

Terminated

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: L-DOS47

• Registration Number: NCT02309892
• Lead Sponsor: Helix BioPharma Corporation

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.

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 Timeline

• Study First Submitted: 2013-04-09
• Study First Submitted QC: 2014-12-03
• Study First Posted: 2014-12-05
• Study Start: 2015-04-20
• Primary Completion: 2019-08-19
• Study Completion: 2019-09-20
• Results First Submitted: 2022-06-29
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-20
• Last Update Submitted: 2023-12-20
• Results First Posted: 2024-06-03
• Last Update Posted: 2024-06-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Pemetrexed and Carboplatin plus L-DOS47	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin.	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
Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin	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.
Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin	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;

Secondary Outcome Measures

Name	Time	Method
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; 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.
Percentage of Patients Receiving a Sustained Clinical Benefit	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).

Trial Locations

Locations (2)

University Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States