Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LY2603618 · 5 trials · 5 indications
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
DLT is defined as adverse event (AE) during Cycle 1 (Days 1 through 28) that was possibly related to the study drug and toxicities considered by the investigator as dose limiting. A summary of other nonserious AEs, and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Urinary and fecal excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in urine and fecal samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in urine and feces.
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-inf)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the cut-off date. OS was summarized using Kaplan-Meier estimates.
| Arm | Type | Description |
|---|---|---|
| LY2603618 and Pemetrexed | EXPERIMENTAL | - |
| LY2603618 | EXPERIMENTAL | Single 50 milligrams (mg) oral dose of desipramine on day 1 of study period 1. Single 275 mg intravenous infusion over one hour of LY2603618 followed by single 50 mg oral dose of desipramine on day 1 of study period 2. Participants may then receive additional doses of LY2603618 in combination as follows: 1000 milligrams per square meter (mg/m²) intravenous administration over 30 minutes of gemcitabine on days 1, 8 and 15 and 230 mg intravenous dose of LY2603618 on days 2, 9 and 16 of 28-day cycles OR 500 mg/m² intravenous administration over 10 minutes of pemetrexed on day 1 and 275 mg intravenous dose of LY2603618 on day 2 of 21-day cycles. Participants will be allowed to continue to receive the combination therapy until fulfilling one of the criteria for discontinuation, such as unacceptable toxicity or disease progression. |
| LY2603618 + Gemcitabine | EXPERIMENTAL | Gemcitabine 1000 milligrams per meter squared (mg/m\^2) administered intravenously on days 1, 8 and 15 of at least one 28-day cycle. 170 or 230 mg LY2603618 administered intravenously on days 2, 9 and 16 of at least one 28-day cycle. Participants experiencing benefit may continue on the combination therapy until discontinuation criteria are met. |
| Gemcitabine | ACTIVE_COMPARATOR | Participants participated in Phase 2 only. Gemcitabine (Phase 2): 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. |
| Name | Type | Description |
|---|---|---|
| LY2603618 | DRUG | 150 milligram per square meter (mg/m\^2) intravenously on Day 2 of each 21 day cycle repeating every 21 days for a minimum of 2 cycles continuing until disease progression |
| Pemetrexed | DRUG | 500 mg/m\^2 intravenously on Day 1 of each 21 Day cycle repeating every 21 days for a minimum of 2 cycles or until disease progression |
| Desipramine | DRUG | Administered orally |
| Gemcitabine | DRUG | Administered intravenously as a 30-minute infusion. |
Inclusion Criteria: * Must agree to have a tumor biopsy at screening * Must have a diagnosis of advanced or metastatic non-squamous non-small cell lung cancer that has progressed after certain prior treatment * Must be available for the duration of the study and willing to follow the study procedur...
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LY2603618 is an investigational small molecule being developed by Eli Lilly and Company for the treatment of cancer. It has been studied in advanced cancer, solid tumors, non small cell lung cancer, and pancreatic neoplasms. It remains in clinical development and is not an approved therapy.
LY2603618 has been studied in advanced cancer, solid tumors, non small cell lung cancer, and pancreatic neoplasms. Clinical testing has included a Phase 2 study in advanced or metastatic non small cell lung cancer and Phase 1 studies in solid tumors, including a combination study with gemcitabine.
LY2603618 is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. The compound is an investigational oncology asset from the company's pipeline and has been evaluated across several cancer indications in early stage clinical testing.
LY2603618 is in Phase 1 development, with one Phase 2 study also conducted. It is investigational and has not been approved by the FDA. The clinical program includes completed Phase 1 and Phase 2 trials, and no trials are currently listed as active.
Completed studies include NCT01358968, a drug interaction study assessing the effect of LY2603618 on the metabolic pathway of desipramine, NCT01341457 in solid tumors in combination with gemcitabine, NCT01296568 in advanced or metastatic solid tumors, and NCT00988858 in advanced or metastatic non small cell lung cancer.
Across its listed clinical trials, LY2603618 has enrolled a total of 157 participants. Individual study sizes ranged from 3 participants in a C14 study in advanced and metastatic solid tumors to 55 participants in a Phase 2 non small cell lung cancer study.