Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LY3537982 · 8 trials · 10 indications
Dose Optimization and Safety Lead-In Part B: Number of Participants with a TEAE
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR)
PK: Cmax of LY3537982
PK: AUC of LY3537982
Part 1: PK: Cmax of LY3537982
Part 1: PK: AUC\[0-inf\] of LY3537982
Part 1: PK: AUClast of LY3537982
Part 1: PK: AUC\[0-inf\] of Digoxin
Part 1: PK: AUC\[0-inf\] of Rosuvastatin
Part 2: PK: AUC\[0-inf\] of LY3537982
Part 2: PK: AUC\[0-inf\] of Midazolam
Part 2: PK: AUC\[0-inf\] of 1'-Hydroxymidazolam
PK: Feur
PK: Fefeces
PK: Feair
PK: F of LY3537982
PK: Cmax of LY3537982 administered with or without itraconazole
PK: AUC\[0-inf\] of LY3537982 administered with or without itraconazole
PK: AUClast of LY3537982 administered with or without itraconazole
PK: AUC\[0-inf\] of LY3537982 administered with or without carbamazepine
PK: AUC(0-inf)
PK: Cmax of LY3537982
Measured by the number of patients with dose-limiting toxicities (DLTs)
Measured by the number of patients with dose-limiting toxicities (DLTs)
Measured by TEAEs
| Arm | Type | Description |
|---|---|---|
| Dose Optimization: LY3537982 Dose Level 1 plus Pembrolizumab | EXPERIMENTAL | LY3537982 Dose level 1 administered orally in combination with pembrolizumab administered intravenously (IV) in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Dose Optimization: LY3537982 Dose Level 2 plus Pembrolizumab | EXPERIMENTAL | LY3537982 Dose level 2 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Safety Lead In: LY3537982 plus Pembrolizumab, Pemetrexed and Platinum | EXPERIMENTAL | LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Part A: LY3537982 plus Pembrolizumab | EXPERIMENTAL | LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Part A: Placebo plus Pembrolizumab | PLACEBO_COMPARATOR | Placebo administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Part B: LY3537982 plus Pembrolizumab, Pemetrexed, and Platinum | EXPERIMENTAL | LY3537982 administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Part B: Placebo plus Pembrolizumab, Pemetrexed, and Platinum | PLACEBO_COMPARATOR | Placebo administered orally in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| Part C: LY3537982 plus Pembrolizumab | EXPERIMENTAL | LY3537982 administered orally in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met. |
| LY3537982 (Normal renal function) | EXPERIMENTAL | LY3537982 administered orally. |
| LY3537982 (Severe renal impairment) | EXPERIMENTAL | LY3537982 administered orally. |
| LY3537982 (Moderate renal impairment) | EXPERIMENTAL | LY3537982 administered orally. |
| LY3537982 | EXPERIMENTAL | LY3537982 administered orally. |
| LY3537982 + Digoxin & Rosuvastatin (Part 1) | EXPERIMENTAL | Single oral doses of digoxin and rosuvastatin with or without multiple doses of LY3537982 administered orally |
| LY3537982 + Midazolam (Part 2) | EXPERIMENTAL | Single doses of midazolam administered either orally or intravenously (IV) with or without multiple doses of LY3537982 administered orally |
| [¹⁴C]-LY3537982 (Part 1) | EXPERIMENTAL | Single dose of \[¹⁴C\]-LY3537982 administered orally. |
| [¹⁴C]-LY3537982 + LY3537982 (Part 2) | EXPERIMENTAL | Single dose of LY3537982 administered orally followed by \[¹⁴C\]-LY3537982 administered intravenously (IV). |
| LY3537982 + Itraconazole (Part 1) | EXPERIMENTAL | LY3537982 administered orally alone followed by LY3537982 administered in combination with itraconazole orally. |
| LY3537982 + Carbamazepine (Part 2) | EXPERIMENTAL | LY3537982 administered orally alone followed by LY3537982 administered in combination with carbamazepine orally. |
| LY3537982 (High-Fat Meal) | EXPERIMENTAL | LY3537982 administered orally under fasting conditions in one study period and under fed conditions (i.e., a standard high-fat meal) in the other study period. |
| LY3537982 (Low-Fat Meal) | EXPERIMENTAL | LY3537982 administered orally under fasting conditions in one study period and under fed conditions (i.e., a standard low-fat meal) in the other study period. |
| LY3537982 (Dose Escalation) | EXPERIMENTAL | LY3537982 administered orally. |
| LY3537982 (Dose Expansion) | EXPERIMENTAL | LY3537982 administered orally either alone or with another investigational agent. |
| LY3537982 (Dose Optimization) | EXPERIMENTAL | LY3537982 administered orally either alone or with another investigational agent |
| Name | Type | Description |
|---|---|---|
| LY3537982 | DRUG | Administered orally. |
| Pembrolizumab | DRUG | Administered IV. |
| Placebo | DRUG | Administered orally. |
| Cisplatin | DRUG | Administered IV. |
| Carboplatin | DRUG | Administered IV. |
| Pemetrexed | DRUG | Administered IV. |
| Digoxin | DRUG | Administered orally |
| Rosuvastatin | DRUG | Administered orally |
| Midazolam | DRUG | Administered orally |
| [¹⁴C]-LY3537982 | DRUG | Administered orally. |
| Itraconazole | DRUG | Administered orally. |
| Carbamazepine | DRUG | Administered orally. |
| Cetuximab | DRUG | Intravenous |
Inclusion Criteria: * Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy. * Part B and Safety Lead-In Part B: the histology of the tumor must be predominantly non-squamous (in line with peme...