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NCT02309892

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

Terminated Phase 1 Results posted Last updated 3 June 2024
What this trial tests

Phase 1 trial testing L-DOS47 in Non-Small Cell Lung Cancer in 14 participants. Terminated before completion.

Timeline
20 April 2015
Primary endpoint
19 August 2019
20 September 2019

Quick facts

Lead sponsorHelix BioPharma Corporation
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment14
Start date20 April 2015
Primary completion19 August 2019
Estimated completion20 September 2019
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Helix BioPharma Corporation

Who can join

18 and older, any sex, with Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Treatment emergent AEs
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin3
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin6
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin2
Treatment emergent AEs related to L-DOS47
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin2
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin5
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Treatment emergent SAEs
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin3
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin1
Treatment emergent SAEs related to L-DOS47
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Number of Participants With Dose Limited Toxicities (DLTs) Related to L-DOS47 in Combination Treatment With Pemetrexed/Carboplatin. Primary · 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

GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Maximum Tolerated Dose of L-DOS47 in Combination With Pemetrexed/Carboplatin Primary · 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.

GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Objective Response Rate of Patients Receiving the Combination Treatment According to RECIST 1.1 Secondary · 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.

Partial response
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin3
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Stable disease
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin2
Progressive disease
GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin2
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin0
Percentage of Patients Receiving a Sustained Clinical Benefit Secondary · 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 lesi

GroupValue95% CI
L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin4
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin1
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin0
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event (AE) reporting period commenced after initial dosing of pemetrexed premedication through 30-day post-last dose of study drug, up to 15 weeks, or longer for those patients who continue on additional treatment cycles. If an AE occurred before first dose of study drug, it would be considered a non-treatment emergent AE. All AEs were followed until resolution/stabilization while patient remained on-study.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

L-DOS47 0.59 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 0/3 (0%)
Deaths: 3/3
L-DOS47 0.78 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 3/6 (50%)
Deaths: 2/6
L-DOS47 1.5 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 0/1 (0%)
Deaths: 0/1
L-DOS47 3.0 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 1/1 (100%)
Deaths: 1/1
L-DOS47 6.0 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 1/1 (100%)
Deaths: 1/1
L-DOS47 9.0 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 1/2 (50%)
Deaths: 1/2
L-DOS47 12.0 ug/kg in Combination With Pemetrexed and Carboplatin
Serious: 0
Deaths: 0

Serious adverse events (13 terms)

ReactionSystemL-DOS47 0.59 ug/kg in Comb…L-DOS47 0.78 ug/kg in Comb…L-DOS47 1.5 ug/kg in Combi…L-DOS47 3.0 ug/kg in Combi…L-DOS47 6.0 ug/kg in Combi…L-DOS47 9.0 ug/kg in Combi…L-DOS47 12.0 ug/kg in Comb…
dyspnoeaRespiratory, thoracic and mediastinal disorders
nauseaGastrointestinal disorders
abdominal painGastrointestinal disorders
vomitingGastrointestinal disorders
loss of consciousnessNervous system disorders
syncopeNervous system disorders
pleural effusionRespiratory, thoracic and mediastinal disorders
pulmonary embolismRespiratory, thoracic and mediastinal disorders
febrile neutropeniaBlood and lymphatic system disorders
neutropeniaBlood and lymphatic system disorders
chest painGeneral disorders
bacteremiaInfections and infestations
platelet count decreasedInvestigations
Other adverse events (85 terms — click to expand)

ReactionSystemL-DOS47 0.59 ug/kg in Comb…L-DOS47 0.78 ug/kg in Comb…L-DOS47 1.5 ug/kg in Combi…L-DOS47 3.0 ug/kg in Combi…L-DOS47 6.0 ug/kg in Combi…L-DOS47 9.0 ug/kg in Combi…L-DOS47 12.0 ug/kg in Comb…
nauseaGastrointestinal disorders
constipationGastrointestinal disorders
oedema peripheralGeneral disorders
fatigueGeneral disorders
chest painGeneral disorders
dyspnoeaRespiratory, thoracic and mediastinal disorders
insomniaPsychiatric disorders
abdominal painGastrointestinal disorders
diarrheaGeneral disorders
pyrexiaGeneral disorders
decreased appetiteMetabolism and nutrition disorders
hypomagnesaemiaMetabolism and nutrition disorders
weight fluctuationMetabolism and nutrition disorders
anaemiaBlood and lymphatic system disorders
rashSkin and subcutaneous tissue disorders
neutrophil count decreasedInvestigations
white blood cell count decreasedInvestigations
hypertensionVascular disorders
headacheNervous system disorders
neuropathy peripheralNervous system disorders
haematuriaRenal and urinary disorders
gastroesophageal refluxGastrointestinal disorders
hyperchlorhydriaGastrointestinal disorders
rectal hemorrhageGastrointestinal disorders
chillsGeneral disorders
facial painGeneral disorders
malaiseGeneral disorders
painGeneral disorders
dehydrationMetabolism and nutrition disorders
dyslipidaemiaMetabolism and nutrition disorders
hyperglycaemiaMetabolism and nutrition disorders
hypocalcaemiaMetabolism and nutrition disorders
hypoglycaemiaMetabolism and nutrition disorders
hypokalaemiaMetabolism and nutrition disorders
increased appetiteMetabolism and nutrition disorders
malnutritionMetabolism and nutrition disorders
epistaxisRespiratory, thoracic and mediastinal disorders
pulmonary embolismRespiratory, thoracic and mediastinal disorders
coughRespiratory, thoracic and mediastinal disorders
pleural effusionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: dyspnoea, nausea, abdominal pain, vomiting, loss of consciousness, syncope, pleural effusion, pulmonary embolism.

Data from ClinicalTrials.gov NCT02309892 adverse events section.

Sponsor's own 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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Emerging therapeutic agents for advanced non-small cell lung cancer.
    Chen R, Manochakian R, James L, Azzouqa AG, et al · · 2020 · cited 244× · PMID 32448366 · DOI 10.1186/s13045-020-00881-7
  2. Causes, consequences, and therapy of tumors acidosis.
    Pillai SR, Damaghi M, Marunaka Y, Spugnini EP, et al · · 2019 · cited 200× · PMID 30911978 · DOI 10.1007/s10555-019-09792-7
  3. Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.
    Alexander E, Leong KW. · · 2024 · cited 83× · PMID 39455963 · DOI 10.1186/s12951-024-02900-y
  4. Targeting acidity in cancer and diabetes.
    Gillies RJ, Pilot C, Marunaka Y, Fais S. · · 2019 · cited 74× · PMID 30708040 · DOI 10.1016/j.bbcan.2019.01.003
  5. Emerging therapeutic agents for lung cancer.
    Dholaria B, Hammond W, Shreders A, Lou Y. · · 2016 · cited 66× · PMID 27938382 · DOI 10.1186/s13045-016-0365-z
  6. The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.
    Garcia-Sampedro A, Gaggia G, Ney A, Mahamed I, et al · · 2021 · cited 31× · PMID 33546207 · DOI 10.3390/jcm10040566
  7. Back to basic: Trials and tribulations of alkalizing agents in cancer.
    Gillies RJ, Ibrahim-Hashim A, Ordway B, Gatenby RA. · · 2022 · cited 21× · PMID 36452492 · DOI 10.3389/fonc.2022.981718

Verify or expand the search:

Other trials of L-DOS47

Trials testing the same drug.

Other recruiting trials for Non-Small Cell Lung Cancer

Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02309892.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing