Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LY3410738 · 4 trials · 9 indications
PK: AUC0-tlast of LY3410738 Tablets Versus Capsules
PK: AUC0-∞ of LY3410738 Tablets Versus Capsules
PK: Cmax of LY3410738 Tablets Versus Capsules
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
For Dose Escalation
For Dose Expansion
| Arm | Type | Description |
|---|---|---|
| Group 1: Tablet versus Capsule | EXPERIMENTAL | Treatment A: LY3410738 capsule on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment B: LY3410738 tablet on Day 4 as a single oral dose in the morning 10 hours prior to and 4 hours after dosing. |
| Group 2: Food Effect Comparison Group | EXPERIMENTAL | Treatment B: LY3410738 table on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment C: LY3410738 table on Day 4 as a single oral dose in the morning 30 minutes after starting a standard low-fat meal. |
| Group 3: Potential of Hydrogen (pH) Effect Fasted Group | EXPERIMENTAL | Treatment B: LY3410738 table on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment D: Esomeprazole single oral dose once daily (QD) in the morning on Days 4 through 8 in fasted state followed by a standard low-fat meal. On Day 9, Esomeprazole a single oral dose followed by LY3410738 tablet as a single oral dose in the morning, following a fast of at least 10 hours prior to and 4 hours after esomeprazole and LY3410738 coadministration. |
| Group 4: pH Effect Fed Group | EXPERIMENTAL | Treatment C: LY3410738 table on Day 1 as a single oral dose in the morning 30 minutes after starting a standard low-fat meal. Treatment E: Esomeprazole as a single oral dose QD in the morning on Days 4 through 8, in fasted state followed by a standard low-fat meal. On Day 9, Esomeprazole as a single oral dose followed by a LY3410738 tablet in the morning in fed state standard low-fat meal. |
| Cohort 1 (Treatment A): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule formulation. |
| Cohort 2 (Treatment B): LY3410738 | PLACEBO_COMPARATOR | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule formulation. |
| Cohort 3 (Treatment C): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule or tablet formulation. |
| Cohort 4 (Treatment D): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule or tablet formulation. |
| Cohort 5 (Treatment E): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule or tablet formulation. |
| Cohort 6 (Treatment F): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule or tablet formulation. |
| Cohort 7 (Treatment G): LY3410738 | EXPERIMENTAL | Single oral dose of LY3410738 or placebo administered as over-encapsulated capsule or tablet formulation. |
| Dose Escalation Arm A (Monotherapy) | EXPERIMENTAL | Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor. |
| Dose Escalation Arm B (Monotherapy) | EXPERIMENTAL | Patients requiring a strong CYP3A4 inhibitor for active management or prevention of a lifethreatening condition, such as an azole administered to prevent invasive fungal infection. |
| Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine) | EXPERIMENTAL | Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738. |
| Cohort 1 | EXPERIMENTAL | Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor. |
| Cohort 2 | EXPERIMENTAL | Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor. |
| Cohort 3 | EXPERIMENTAL | Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation. |
| Cohort 4 | EXPERIMENTAL | Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations. |
| Cohort 5 | EXPERIMENTAL | Patients with newly diagnosed AML, R/R AML, or other advanced hematologic malignancy harboring IDH1 and/or IDH2 mutations with no prior venetoclax therapy. Strong CYP3A4 inhibitor allowed but not required. |
| LY3410738 | EXPERIMENTAL | Phase 1 dose escalation - Multiple doses of LY3410738 |
| LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab | EXPERIMENTAL | Phase 1 dose expansion - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of LY3410738 alone or in combination with gemcitabine plus cisplatin or in combination with durvalumab |
| Name | Type | Description |
|---|---|---|
| LY3410738 | DRUG | Administered orally. |
| Esomeprazole | DRUG | Administered orally. |
| Placebo | DRUG | Administered orally. |
| Venetoclax | DRUG | Oral venetoclax |
| Azacitidine | DRUG | Subcutaneous or intravenous azacitidine |
| Gemcitabine | DRUG | Intravenous gemcitabine |
| Cisplatin | DRUG | Intravenous cisplatin |
| Durvalumab | DRUG | Intravenous durvalumab |
Inclusion Criteria: * Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m\^2), inclusive. * Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign m...