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

NCT02309892 | Terminated Phase 1 Results DMC

• 1 other identifier: LDOS001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Neoplasms; Immunoconjugate; Tumor microenvironment alkalinization

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Treatment Emergent Adverse Events as a Measure Safety and Tolerability of L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin

  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.

  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

  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 Outcomes (2)

• Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1

  Up to 12 weeks

• Percentage of Patients Receiving a Sustained Clinical Benefit

  Up to 12 weeks

Study Arms (1)

Pemetrexed and Carboplatin plus L-DOS47

EXPERIMENTAL

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

Interventions

L-DOS47 DRUG

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.

Pemetrexed and Carboplatin plus L-DOS47

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Helix BioPharma Corporation: lead
• Theradex: collaborator

Study Sites (2)

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Location

Related Links

• Helix BioPharma corporate website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Patient enrolment was halted at cohort 6 (9.0 ug/kg) due to slow recruitment and therefore, the seventh and highest dosing cohort (12 ug/kg) could not be completed.

Results Point of Contact

• Title: Brenda Lee, Director, Clinical Operations
• Organization: Helix BioPharma Corp.

blee@helixbiopharma.com

416 642 1807

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, dose escalation where patients are recruited into cohorts of escalating doses of L-DOS47 (0.59 up to 12.0 µg/kg) in combination with pemetrexed and carboplatin.

Study Record Dates

• First Submitted: April 9, 2013
• First Posted: December 5, 2014
• Study Start: April 20, 2015
• Primary Completion: August 19, 2019
• Study Completion: September 20, 2019
• Last Updated: June 3, 2024
• Results First Posted: June 3, 2024

Record last verified: 2023-12

Locations

US (2)