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NCT02735980

A Study of Prexasertib (LY2606368) in Participants With Extensive Stage Disease Small Cell Lung Cancer

Completed Phase 2 Results posted Last updated 17 March 2020
What this trial tests

Phase 2 trial testing Prexasertib in Small Cell Lung Cancer in 133 participants. Completed in 12 February 2019.

Timeline
11 May 2016
Primary endpoint
31 July 2017
12 February 2019

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment133
Start date11 May 2016
Primary completion31 July 2017
Estimated completion12 February 2019
Sites41 locations across France, Netherlands, Greece, Ukraine, United Kingdom, Germany, South Korea, United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with 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.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) Primary · Baseline to 10 months

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions

GroupValue95% CI
Prexasertib (Platinum Sensitive Disease)5.20.7 – 9.6
Prexasertib (Platinum Resistant Disease)00.0 – 3.7
Prexasertib Exploratory Addendum (Platinum Sensitive Disease)00.0 – 14.8
Pharmacokinetics(PK): Maximum Concentration (Cmax) of Prexasertib Cohort 1 and Cohort 2 Secondary · Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Pharmacokinetics(PK): Maximum Concentration of Prexasertib. The same dose was administered to Cohort 1 and Cohort 2 and were combined for analysis.

Cycle 1
GroupValue95% CI
105 mg/m^2 Prexasertib722± 64
Cycle 3
GroupValue95% CI
105 mg/m^2 Prexasertib735± 71
Cycle 5
GroupValue95% CI
105 mg/m^2 Prexasertib732± 69
Cycle 7
GroupValue95% CI
105 mg/m^2 Prexasertib1230± 22
Pharmacokinetics(PK): Maximum Concentration of Prexasertib Cohort 3 (40 mg/m^2, Protocol Addenda) Secondary · Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Pharmacokinetics(PK): Maximum Concentration of Prexasertib

GroupValue95% CI
40 mg/m2 Prexasertib Exploratory Addendum227± 68
Pharmacokinetics: Area Under the Concentration Curve of Prexasertib Secondary · Cycle 1,3, 5, and 7: Day 1, Day 2 and Day 3- Prior to start of infusion, end of infusion plus 10 minutes, Day 8: anytime

Pharmacokinetics: Area Under the Concentration Curve of Prexasertib

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)126± 154
Cohort 2 Prexasertib (Platinum Resistant Disease)1190± 95
Cohort 3 Prexasertib Exploratory(Platinum Sensitive Disease)1840± 35
Disease Control Rate: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) Secondary · Baseline through Disease Progression or Death from Any Cause to 28 months

Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)3112.6 – 31.4
Cohort 2 Prexasertib (Platinum Resistant Disease)20.06.6 – 20.6
Cohort 3 Prexasertib Exploratory(Platinum Sensitive Disease)40.010.2 – 48.4
Progression-Free Survival (PFS) Secondary · Baseline to Disease Progression or Death (up to 9 months)

PFS defined as the from randomization date to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progre

GroupValue95% CI
Prexasertib (Platinum Sensitive Disease)1.411.31 – 1.64
Prexasertib (Platinum Resistant Disease)1.361.25 – 1.45
Prexasertib Exploratory Addendum (Platinum Sensitive Disease)1.581.38 – 3.12
Duration of Response (DoR) Secondary · Date of CR or PR to Date of Disease Progression or Death Due to Any Cause up to 9 months

DoR the time from the date of an objective response until Progressive Disease (PD): was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)NA
Cohort 2 Prexasertib (Platinum Resistant Disease)NA
Cohort 3 Prexasertib Exploratory(Platinum Sensitive Disease)NA
Overall Survival (OS) Secondary · Baseline up to 28 months

OS defined as from randomization date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)5.423.75 – 8.51
Cohort 2 Prexasertib (Platinum Resistant Disease)3.152.27 – 5.52
Cohort 3 Prexasertib Exploratory(Platinum Sensitive Disease)7.262.00 – 9.49
Change From Baseline in Lung Cancer Symptom Scale Score (LCSS) Secondary · Baseline up to 9 months

LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)-2.8± 12.3
Cohort 2 Prexasertib (Platinum Resistant Disease)-4.0± 10.2
Change From Baseline on the Average Symptom Burden Index (ASBI) Secondary · Baseline up to 9 months

ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).

GroupValue95% CI
Cohort 1 Prexasertib (Platinum Sensitive Disease)-3.0± 11.9
Cohort 2 Prexasertib (Platinum Resistant Disease)-4.4± 11.1

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 28 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

105 mg/m^2 Prexasertib (Platinum Sensitive Disease)
Serious: 21/56 (38%)
Deaths: 10/56
105 mg/m^2 Prexasertib (Platinum Resistant Disease)
Serious: 16/60 (27%)
Deaths: 7/60
40 mg/m2 Prexasertib Exploratory Addendum
Serious: 6/15 (40%)
Deaths: 11/15

Serious adverse events (52 terms)

ReactionSystem105 mg/m^2 Prexasertib (Pl…105 mg/m^2 Prexasertib (Pl…40 mg/m2 Prexasertib Explo…
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Platelet count decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
BronchitisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Mental status changesPsychiatric disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
Abdominal painGastrointestinal disorders
AscitesGastrointestinal disorders
Colitis ischaemicGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Multiple organ dysfunction syndromeGeneral disorders
PainGeneral disorders
Device related infectionInfections and infestations
Escherichia bacteraemiaInfections and infestations
Other adverse events (63 terms — click to expand)

ReactionSystem105 mg/m^2 Prexasertib (Pl…105 mg/m^2 Prexasertib (Pl…40 mg/m2 Prexasertib Explo…
AnaemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
White blood cell count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ThrombocytopeniaBlood and lymphatic system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
ConstipationGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Lymphocyte count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
LeukopeniaBlood and lymphatic system disorders
DehydrationMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Weight decreasedInvestigations
HeadacheNervous system disorders
Oedema peripheralGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Productive coughRespiratory, thoracic and mediastinal disorders
StomatitisGastrointestinal disorders
Urinary tract infectionInfections and infestations
HyperuricaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Bone painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Platelet count decreased, Dyspnoea, Sepsis, Anaemia, Thrombocytopenia, Fatigue.

Data from ClinicalTrials.gov NCT02735980 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety and efficacy of prexasertib when given to participants with extensive stage disease small cell lung cancer (ED-SCLC). The study will evaluate how the body processes the drug and how the drug affects the body. The study will also evaluate the association between tumor response and the participant's perceived quality of life.

Publications & conference data

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

  1. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
    Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
  2. ATR/CHK1 inhibitors and cancer therapy.
    Qiu Z, Oleinick NL, Zhang J. · · 2018 · cited 282× · PMID 29054375 · DOI 10.1016/j.radonc.2017.09.043
  3. Targeting the ATR-CHK1 Axis in Cancer Therapy.
    Rundle S, Bradbury A, Drew Y, Curtin NJ. · · 2017 · cited 173× · PMID 28448462 · DOI 10.3390/cancers9050041
  4. CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib.
    Sen T, Tong P, Stewart CA, Cristea S, et al · · 2017 · cited 166× · PMID 28490518 · DOI 10.1158/0008-5472.can-16-3409
  5. DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities.
    Abuetabh Y, Wu HH, Chai C, Al Yousef H, et al · · 2022 · cited 159× · PMID 36207426 · DOI 10.1038/s12276-022-00863-4
  6. Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy.
    Knudsen ES, Pruitt SC, Hershberger PA, Witkiewicz AK, et al · · 2019 · cited 145× · PMID 31174843 · DOI 10.1016/j.trecan.2019.03.005
  7. New Approaches to SCLC Therapy: From the Laboratory to the Clinic.
    Poirier JT, George J, Owonikoko TK, Berns A, et al · · 2020 · cited 141× · PMID 32018053 · DOI 10.1016/j.jtho.2020.01.016
  8. Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation.
    Topatana W, Juengpanich S, Li S, Cao J, et al · · 2020 · cited 128× · PMID 32883316 · DOI 10.1186/s13045-020-00956-5

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Trials by the same sponsor.

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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/NCT02735980.

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