Ovarian Cancer, Non Small Cell Lung Cancer, Prostate Cancer, Colorectal Cancer, Gastric Cancer, Esophageal Cancer, Cancer of Head and Neck
Conditions
Brief summary
The purpose of the study is to estimate the rate of response for patients with ovarian, non-small cell lung, prostate, colorectal, gastroesophageal, and head and neck cancers who are administered LY2523355.
Interventions
DRUGLY2523355
Dose determined by participant body surface area: 5 milligrams/square meter(mg/m²) or 6 mg/m², administered intravenously as a 1-hour infusion on Days 1, 2 and 3 of a 21 day cycle; for up to 2 cycles (4 cycles for prostate cancer patients). Additional cycles administered based on patient response assessment.
DRUGpegfilgrastim
6 milligrams (mg), administered subcutaneously approximately 24 hours after third dose of LY2523355 on Day 4 of each 21-day cycle, for up to 2 cycles of LY2523355 administration (4 cycles for prostate cancer patients). Additional cycles of LY2523355 administered based on patient response assessment.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ovarian, non-small cell lung, prostate, colorectal, gastroesophageal cancer (adenocarcinoma of the esophageal cancer, stomach, or gastroesophageal junction), or squamous cell cancer of the head and neck * Have measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines (except prostate cancer participants) * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Are willing to follow study procedures for the duration of the study * Are willing to use an approved contraceptive method during treatment and for 3 months after discontinuation of study treatment
Exclusion criteria
* Have a serious preexisting medical condition that would preclude participation in the study * Are pregnant or lactating * Have received treatment within 28 days of first dose of LY2523355 with a drug that has not received regulatory approval for any indication * Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases * Have a second active primary malignancy or a history of a second malignancy requiring cytotoxic therapy * Have QTc interval greater than 470 millisecond (msec) or intraventricular conduction delay (IVCD) with QRS greater than 120 msec on screening electrocardiogram (ECG) * Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral (A, B, C) hepatitis * Participants with pneumonia, evidence of obstructive pneumonitis, other respiratory infections, or infection from other sources are to be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Baseline until progressive disease up to 36 weeks post-baseline | The percentage of participants who achieved a best response of either CR or PR, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Percentage is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Date of enrollment to progressive disease or death due to any cause up to 36 weeks post-enrollment | PFS defined as the time from date of first dose to the first observation of disease progression or death due to any cause. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 millimeter (mm) increase over nadir. For participants who were not known to have died or to have progressed as of the data inclusion cutoff date, PFS were censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. |
| Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Baseline until progressive disease up to 36 weeks post-baseline | Response using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria. |
| Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | Baseline | The number of participants with colorectal cancer (CRC), gastroesophageal cancer (GE), non-small cell lung cancer (NSCLC), ovarian cancer, prostate cancer or squamous cell carcinoma of head and neck (SCCHN) who had marker/molecular diagnostics performed prior to study entry to determine the mutation status of cancer genes: APC, BRAF, BRCA1, BRCA2, HRAS and KRAS and the presence of Human Papillovirus (HPV) and Epstein Barr viruses (EBV). Mutation/virus status was defined as: positive (mutation/virus present), negative (mutation/virus not present), unknown (mutation/virus status unknown), or not done (mutation/virus status was not done). |
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | Day 3 of Cycle 1 (21-day cycle) | Plasma Cmax following daily doses of LY2523355 on Days 1, 2, and 3 of Cycle 1 (21-day cycle). |
| Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355 | Day 1 and Day 3 of Cycle 1 (21-day cycle) | Intracycle Ra of LY2523355 is the ratio of LY2523355 maximum plasma concentration (Cmax) on Day 3 of Cycle 1 to the Cmax of LY2523355 on Day 1 of Cycle 1 following daily doses of LY2523355 on Days 1, 2 and 3 of Cycle 1 (21-day cycle) at each dose level. |
| Change in Tumor Size at Smallest Size (Best Response) | Baseline until cycle with maximum change from baseline up to 36 weeks | The percent change in tumor size at its smallest size. The sum of diameters of target lesions was determined at each tumor assessment. The percent change is the smallest post-baseline sum divided by the baseline (pre-treatment) sum, multiplied by 100. |
Other
| Measure | Time frame |
|---|---|
| Number of Participants Who Died Due to Unknown Causes During the 30-Day Post-Study Treatment Follow-Up | End of study treatment up to 30-days post-study treatment discontinuation |
Countries
United States
Participant flow
Pre-assignment details
All participants who received at least one dose of study drug in both Cycle 1 and Cycle 2 or to have progressed or died on or before study Day 42 were considered to be completed.
Participants by arm
| Arm | Count |
|---|---|
| LY2523355 LY2523355: Dose determined by participant body surface area: 5 milligrams/square meter(mg/m²) or 6 mg/m², administered intravenously as a one hour infusion on Days 1, 2 and 3 of a 21 day cycle for up to 2 cycles (4 cycles for prostate cancer participants). Additional cycles administered based on participant response assessment.
Pegfilgrastim: 6 milligrams (mg), administered subcutaneously approximately 24 hours after third dose of LY2523355 on Day 4 of each 21-day cycle, for up to 2 cycles of LY2523355 administration (4 cycles for prostate cancer participants). Additional cycles of LY2523355 administered based on participant response assessment. | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | LY2523355 |
|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 93 Participants |
| Region of Enrollment United States | 103 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 70 Participants |
| Tumor Type Colorectal Cancer | 17 participants |
| Tumor Type Gastroesophageal Cancer | 13 participants |
| Tumor Type Non-Small Cell Lung Cancer | 29 participants |
| Tumor Type Ovarian Cancer | 13 participants |
| Tumor Type Prostate Cancer | 18 participants |
| Tumor Type Squamous Cell Carcinoma of the Head and Neck | 13 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 102 / 103 |
| serious Total, serious adverse events | 39 / 103 |
Outcome results
Primary
Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
The percentage of participants who achieved a best response of either CR or PR, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Percentage is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Time frame: Baseline until progressive disease up to 36 weeks post-baseline
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Colorectal Cancer | 0 percentage of participants |
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Gastroesophageal Cancer | 0 percentage of participants |
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Non-Small Cell Lung Cancer | 0 percentage of participants |
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Ovarian Cancer | 0 percentage of participants |
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Prostate Cancer | 0 percentage of participants |
| LY2523355 | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Squamous Cell Carcinoma of Head and Neck | 0 percentage of participants |
Secondary
Change in Tumor Size at Smallest Size (Best Response)
The percent change in tumor size at its smallest size. The sum of diameters of target lesions was determined at each tumor assessment. The percent change is the smallest post-baseline sum divided by the baseline (pre-treatment) sum, multiplied by 100.
Time frame: Baseline until cycle with maximum change from baseline up to 36 weeks
Population: All enrolled participants who received at least 1 dose of study drug with results at baseline and at time of best response.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Colorectal Cancer | 15.4 percentage of change | Standard Deviation 17.12 |
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Gastroesophageal Cancer | 29.0 percentage of change | Standard Deviation 70 |
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Non-Small Cell Lung Cancer | 21.9 percentage of change | Standard Deviation 48.69 |
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Ovarian Cancer | 22.1 percentage of change | Standard Deviation 31.4 |
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Prostate Cancer | 12.2 percentage of change | Standard Deviation 15.91 |
| LY2523355 | Change in Tumor Size at Smallest Size (Best Response) | Squamous Cell Carcinoma of Head and Neck | 3.9 percentage of change | Standard Deviation 30.67 |
Secondary
Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
Response using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria.
Time frame: Baseline until progressive disease up to 36 weeks post-baseline
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Colorectal Cancer | 37.5 percentage of participants |
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Gastroesophageal Cancer | 16.7 percentage of participants |
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Non-Small Cell Lung Cancer | 38.5 percentage of participants |
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Ovarian Cancer | 30.8 percentage of participants |
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Prostate Cancer | 47.1 percentage of participants |
| LY2523355 | Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Squamous Cell Carcinoma of Head and Neck | 50.0 percentage of participants |
Secondary
Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355
Intracycle Ra of LY2523355 is the ratio of LY2523355 maximum plasma concentration (Cmax) on Day 3 of Cycle 1 to the Cmax of LY2523355 on Day 1 of Cycle 1 following daily doses of LY2523355 on Days 1, 2 and 3 of Cycle 1 (21-day cycle) at each dose level.
Time frame: Day 1 and Day 3 of Cycle 1 (21-day cycle)
Population: All enrolled participants who received at least 1 dose of study drug with Ra measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2523355 | Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355 | 1.02 ratio | Geometric Coefficient of Variation 87 |
| 6 mg/m² LY253355 | Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355 | 1.08 ratio | Geometric Coefficient of Variation 61 |
Secondary
Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307
Plasma Cmax following daily doses of LY2523355 on Days 1, 2, and 3 of Cycle 1 (21-day cycle).
Time frame: Day 3 of Cycle 1 (21-day cycle)
Population: All enrolled participants who received at least 1 dose of study drug with Cmax measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2523355 | Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | LSN2546307 | 5.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| LY2523355 | Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | LY2523355 | 125 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79 |
| 6 mg/m² LY253355 | Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | LY2523355 | 124 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67 |
| 6 mg/m² LY253355 | Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | LSN2546307 | 5.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
Secondary
Progression Free Survival (PFS)
PFS defined as the time from date of first dose to the first observation of disease progression or death due to any cause. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 millimeter (mm) increase over nadir. For participants who were not known to have died or to have progressed as of the data inclusion cutoff date, PFS were censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy.
Time frame: Date of enrollment to progressive disease or death due to any cause up to 36 weeks post-enrollment
Population: All enrolled participants who received at least 1 dose of study drug. Percentage (%) of participants censored were colorectal cancer 5.9%; gastroesophageal cancer 0.0%, non-small cell lung cancer 3.4%, ovarian cancer 15.4%, prostate cancer 16.7%, and squamous cell carcinoma of the head and neck 15.4%.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LY2523355 | Progression Free Survival (PFS) | Colorectal Cancer | 1.30 months |
| LY2523355 | Progression Free Survival (PFS) | Gastroesophageal Cancer | 1.25 months |
| LY2523355 | Progression Free Survival (PFS) | Non-Small Cell Lung Cancer | 1.31 months |
| LY2523355 | Progression Free Survival (PFS) | Ovarian Cancer | 1.31 months |
| LY2523355 | Progression Free Survival (PFS) | Prostate Cancer | 2.30 months |
| LY2523355 | Progression Free Survival (PFS) | Squamous Cell Carcinoma of Head and Neck | 1.51 months |
Secondary
Tumor Marker Values as Relevant to Specific Tumor Types at Baseline
The number of participants with colorectal cancer (CRC), gastroesophageal cancer (GE), non-small cell lung cancer (NSCLC), ovarian cancer, prostate cancer or squamous cell carcinoma of head and neck (SCCHN) who had marker/molecular diagnostics performed prior to study entry to determine the mutation status of cancer genes: APC, BRAF, BRCA1, BRCA2, HRAS and KRAS and the presence of Human Papillovirus (HPV) and Epstein Barr viruses (EBV). Mutation/virus status was defined as: positive (mutation/virus present), negative (mutation/virus not present), unknown (mutation/virus status unknown), or not done (mutation/virus status was not done).
Time frame: Baseline
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | CRC-BRAF Mutation, Negative | 2 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | CRC-BRAF Mutation, Not Done/Unknown | 15 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | CRC-KRAS Mutation, Positive | 9 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | CRC-KRAS Mutation, Negative | 7 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | CRC-KRAS Mutation, Not Done | 1 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | GE-KRAS Mutation, Negative | 1 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | GE-KRAS Mutation, Not Done/Unknown | 12 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | NSCLC-KRAS Mutation, Positive | 3 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | NSCLC-KRAS Mutation, Negative | 5 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | NSCLC-KRAS Mutation, Not Done/Unknown | 21 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | Ovarian-BRCA1 Mutation, Negative | 3 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | Ovarian-BRCA1 Mutation, Not Done/Unknown | 10 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | Ovarian-BRCA2 Mutation, Negative | 3 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | Ovarian-BRCA2 Mutation, Not Done/Unknown | 10 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | SCCHN-APC Mutation, Negative | 1 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | SCCHN-APC Mutation, Not Done/Unknown | 12 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | SCCHN-HPV (HPV-31 Positive) Mutation | 1 Participants |
| LY2523355 | Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | SCCHN-HPV Mutation, Not Done/Unknown | 12 Participants |
Other Pre-specified
Number of Participants Who Died Due to Unknown Causes During the 30-Day Post-Study Treatment Follow-Up
Time frame: End of study treatment up to 30-days post-study treatment discontinuation
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LY2523355 | Number of Participants Who Died Due to Unknown Causes During the 30-Day Post-Study Treatment Follow-Up | 5 Participants |