A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47

NCT02340208 | Completed Phase 1 DMC

• 1 other identifier: LDOS002
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

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 patients with non-squamous non-small cell lung cancer when given as a monotherapy.

Conditions

Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47

  Assessed during the AE reporting period starts on Cycle 1 Day 1 up to the last study visit.

  Up to 12 weeks

Secondary Outcomes (4)

• L-DOS47 related toxicity during the first 2 hours after infusion

  During the first 2 hours after infusion

• The incidence and severity of all reported adverse events and serious adverse events

  Participants will be followed for 12 weeks and the 30 day follow-up period

• Changes from baseline for additional safety parameters (clinical laboratory assessments, vital signs, weight, oxygen requirement and 12-lead ECG)

  Up to 12 weeks

• The evaluation of anti-L-DOS47 antibody over time

  Up to 12 weeks

Other Outcomes (4)

• Maximum observed plasma concentration (Cmax) of L-DOS47 at each dose level

  Up to 12 weeks

• Time to maximum observed plasma concentration (Tmax) of L-DOS47 at each dose level

  Up to 12 weeks

• Area under the concentration (AUC) vs time curve of L-DOS47 at each dose level

  Up to 12 weeks

Study Arms (1)

L-DOS47

EXPERIMENTAL

Patient 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 0.12 μg/kg; further possible dose levels include 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45, 3.26 and 4.33 μg/kg.

Drug: L-DOS47

Interventions

L-DOS47 DRUG

A treatment cycle will be 21 days with patients receiving L-DOS47 on cycle Days 1 and 8.

L-DOS47

Eligibility Criteria

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

You may qualify if:

• Patients will be entered in the study only if they meet all of the following criteria:
• Male or female aged ≥ 18 years old
• Have histologically confirmed non-squamous NSCLC that are:
• Chemo naïve Stage IIIb or IV non-squamous NSCLC who are not candidates for chemotherapy or radiotherapy, or who refused standard therapy
• Refractory Stage IIIb or IV non-squamous NSCLC. (Staging of non-squamous NSCLC must be assessed according to TNM, 7th edition and based on computed tomography (CT) scan.)
• Have at least a single measurable lesion in accordance with the RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
• Have a life expectancy of ≥ 3 months
• Have adequate bone marrow, renal and liver function

You may not qualify if:

• Are pregnant or nursing mother
• Have a prior history of other malignancies with the exception of non melanoma skin cancer
• Have known history of central nervous system (CNS) metastatic disease (previously treated or untreated)
• Show evidence of active infection
• Have received treatment in another clinical study within the 30 days before commencing study drug or have not recovered from side effects of a study drug, except for alopecia
• Have a serious uncontrolled medical condition
• Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
• Sustained QTc (QT interval corrected for heart rate) with Fridericia's correction \> 450 ms at screening, or a history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome)
• Pre-existing peripheral neuropathy ≥ CTC Grade 2
• Have dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol
• Are receiving chemotherapy during the 30 days before study treatment start; are receiving radiotherapy, targeted therapy, hormonal therapy, immunotherapy, major surgery or other study drugs during the 4 weeks before study treatment start, or have not recovered from all treatment related toxicities to Grade ≤ 1, except for alopecia. (Radiotherapy is allowed for the symptomatic treatment of bone metastases.)
• Are taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
• Are participating (or planning to participate) in any other clinical trial during this study.

Sponsors & Collaborators

• Helix BioPharma Corporation: lead
• Pharm-Olam International: collaborator

Study Sites (5)

Mazovian Center of Pulmonary Diseases and Tuberculosis

Otwock, Poland

Location

Med. Polonia Hospital Poznan

Poznan, Poland

Location

Institute of Tuberculosis and Lung Diseases

Warsaw, Poland

Location

Military Medical Institute

Warsaw, Poland

Location

The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology

Warsaw, Poland

Location

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

Study Officials

• Dariusz Kowalski, MD, PhD

  The Maria Sklodowska-Curie Memorial Cancer Centre & Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: January 16, 2015
• Study Start: May 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: December 20, 2017
• Last Updated: March 14, 2019

Record last verified: 2019-03

Locations

PL (5)