Description:
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.
Title
- Brief Title: A Dose Escalation Study of L-DOS47 in Recurrent or Metastatic Non-Squamous NSCLC
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
LDOS001
- NCT ID:
NCT02309892
Conditions
- Non-Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
L-DOS47 | | Pemetrexed and Carboplatin plus L-DOS47 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. 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. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin |
Time Frame: | Participants will be followed for 12 weeks |
Safety Issue: | |
Description: | The AE reporting period starts on Cycle 1 Day 1 up to the last study visit. |
Secondary Outcome Measures
Measure: | Objective response rate of patients receiving the combination treatment according to RECIST 1.1 |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Number of patient receiving a sustained clinical benefit |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Defined as the percentage of patients who have achieved complete response, partial response, and stable disease following combination treatment with L-DOS47 + pemetrexed/carboplatin. |
Measure: | Maximum observed plasma concentration (Cmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47 |
Measure: | Time to maximum observed plasma concentration (Tmax) of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47 |
Measure: | Area under the concentration (AUC) vs time curve of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47 |
Measure: | Terminal elimination half-life of L-DOS47 after dosing in combination treatment with pemetrexed/carboplatin |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Pharmacokinetic parameters for L-DOS47 will be determined from plasma samples collected from all patients dosed with L-DOS47 |
Measure: | The presence of anti-L-DOS47 antibodies for patients dosed with L-DOS47 in combination treatment with pemetrexed/carboplatin |
Time Frame: | Up to 12 weeks |
Safety Issue: | |
Description: | Serum samples will be collected and analyzed from all patients dosed with L-DOS47 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Helix BioPharma Corporation |
Trial Keywords
- Non-Small Cell Lung Cancer
- Neoplasms
- Immunoconjugate
- Tumor microenvironment alkalinization
Last Updated
February 24, 2020