A Phase 1 Study in Patients With Solid Tumors

Eksperimentel: Experimental: Pemetrexed followed by LY573636

Pemetrexed on Day 1 followed by LY573636 on Day 4

Medicin: LY573636

Individualized dose is dependent on a patient's height, weight, and gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid [350 micrograms (µg) to 1000 µg orally, daily], Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone [4 milligrams (mg) orally, twice daily or equivalent].

Andre navne:

• Tasisulam

Medicin: Pemetrexed

375 to 500 milligrams per square meter (mg/m^2), intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid (350 µg to 1000 µg orally, daily), Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone (4 mg orally, twice daily or equivalent).

Andre navne:

• Alimta
• LY231514

Eksperimentel: Experimental: LY573636 followed by Pemetrexed

LY573636 on Day 1, pemetrexed on Day 4

Medicin: LY573636

Individualized dose is dependent on a patient's height, weight, and gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid [350 micrograms (µg) to 1000 µg orally, daily], Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone [4 milligrams (mg) orally, twice daily or equivalent].

Andre navne:

• Tasisulam

Medicin: Pemetrexed

375 to 500 milligrams per square meter (mg/m^2), intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid (350 µg to 1000 µg orally, daily), Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone (4 mg orally, twice daily or equivalent).

Andre navne:

• Alimta
• LY231514

Eksperimentel: Experimental: LY573636 and Pemetrexed on Day 1

LY573636 and Pemetrexed on Day 1

Medicin: LY573636

Individualized dose is dependent on a patient's height, weight, and gender and is adjusted to target a specific exposure range corrected for a patient's laboratory parameters. Intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid [350 micrograms (µg) to 1000 µg orally, daily], Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone [4 milligrams (mg) orally, twice daily or equivalent].

Andre navne:

• Tasisulam

Medicin: Pemetrexed

375 to 500 milligrams per square meter (mg/m^2), intravenous dosing is completed once per cycle (cycle equals either 21 or 28 days).

Patients may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.

Patients are pretreated with folic acid (350 µg to 1000 µg orally, daily), Vitamin B12 (1000 µg intramuscular injection every 9 weeks), and dexamethasone (4 mg orally, twice daily or equivalent).

Andre navne:

• Alimta
• LY231514

Recommended Phase 2 Dose

Based on maximum tolerated dose (MTD) in Cycle 1: highest dose where <33% participants (pts) had dose-limiting toxicity (DLT). DLTs were adverse events (AE) possibly related to study drug or AEs that met any of National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTAE): Grade (G) 4 neutropenia lasting ≥5 days; G4 neutropenia with fever, G4 thrombocytopenia, G3 thrombocytopenia with bleeding, ≥G3 non-hematologic toxicity (except nausea/vomiting and diarrhea controlled by medication; electrolyte toxicity resolved with standard replacement treatment; alopecia; and elevated alanine aminotransferase or aspartate aminotransferase with preexisting hepatic metastasis, if agreed by investigator). Investigators, with sponsor, could declare a DLT if pt experienced increasing toxicity during treatment and it was clear that further treatment would expose pt to excessive risk. Enrollment was stopped during the dose-escalation phase, thus further dose-escalation was not explored.

Number of Participants With Clinically Significant Effects

Clinically significant effects were defined as serious and other non-serious adverse events (AEs) regardless of causality. A summary of serious and all other non-serious AEs is located in the Reported Adverse Events module.

Percentage of Participants With a Tumor Response

Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and confirmed by repeat assessment. Complete Response (CR) was defined as the disappearance of all target lesions and the normalization of tumor marker levels for non-target lesions; Partial Response (PR) was defined as at least a 30% decrease in the sum of the longest diameter of target lesions. Percentage of participants with a tumor response = (number of participants with CR or PR/number of enrolled participants)*100.

Pharmacokinetics, Concentration Maximum (Cmax) of LY573636

Pharmacokinetics, Area Under the Curve (AUC) of LY573636

Area under the concentration-time curve above the albumin corrected threshold (AUCalb) is provided for LY573636, which has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.