Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [¹⁴C]Prexasertib, LY2606368
Prexasertib · 10 trials · 30 indications
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review 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 non-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 per cohort with at least 1 measurable lesion, multiplied by 100.
ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions
The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days).
Incidence of adverse event data at least possibly related to treatment will be summarized in tables by treatment combination and by dose level.
Prexasertib area under the curve (AUC0-∞) is estimated based on course 1, days 2 through 7 PK samples.
Prexasertib systemic clearance (CL) is estimated based on course 1, days 2 through 7 pharmacokinetic samples.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
| Arm | Type | Description |
|---|---|---|
| Prexasertib Cohort 1 | EXPERIMENTAL | Participants received 105 milligram per square meter (mg/m²) prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, breast cancer susceptibility gene (BRCA) negative and have received ≥3 lines of prior therapy. |
| Prexasertib Cohort 2 | EXPERIMENTAL | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA negative and have received \<3 lines of prior therapy. |
| Prexasertib Cohort 3 | EXPERIMENTAL | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum-resistant disease, BRCA positive and received a prior poly ADP ribose polymerase (PARP) inhibitor. |
| Prexasertib Cohort 4 | EXPERIMENTAL | Participants received 105 mg/m² prexasertib as an approximately 60 (+10) minute IV infusion on Day 1 and 15 of a 28-day cycle. Participants were with platinum refractory disease, BRCA positive or negative, no restriction on number of lines of prior therapy. |
| Prexasertib (Platinum Sensitive Disease) | EXPERIMENTAL | 105 mg/m\^2 Intravenous (IV) prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had platinum-sensitive disease (has prior platinum based therapy with subsequent progression greater or less than 90 days after last dose of platinum based therapy). |
| Prexasertib (Platinum Resistant Disease) | EXPERIMENTAL | 105 mg/m\^2 IV prexasertib administered of every 14 days with extensive stage disease small cell lung cancer (ED-SCLC) who had resistant/refractory disease (did not have an objective response to platinum-based therapy or had progression greater than 90 days after the last dose of platinum). |
| Prexasertib Exploratory Addendum (Platinum Sensitive Disease) | EXPERIMENTAL | 40 mg/m\^2 IV prexasertib Day 1, 2, and Day 3 of a 14 day cycle in participants with ED-SCLC platinum sensitive disease. |
| A: prexasertib + cyclophosphamide | EXPERIMENTAL | Stratum A: Participants receive combination treatment with cyclophosphamide given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, cyclophosphamide may be given on day 16 and prexasertib may be given on day 17. |
| B: prexasertib + gemcitabine | EXPERIMENTAL | Stratum B: Participants receive combination treatment with gemcitabine given intravenously (IV) on days 1 and 15 and prexasertib given intravenously (IV) on days 2 and 16. Cycles repeat every 28 days for up to 24 months (26 cycles) in the absence of disease progression or unacceptable toxicity. They may also receive growth therapy support with filgrastim or peg-filgrastim. Note: Only if absolutely necessary, gemcitabine may be given on day 16 and prexasertib may be given on day 17. |
| Prexasertib Combine with Olaparib | EXPERIMENTAL | * Olaparib will be administered orally on an intermittent schedule during each 28-day cycle. Exact administration schedule will depend on assigned dose level. * Prexasertib will be administered intravenously on Days 1 and 15 of a cycle |
| [¹⁴C]Prexasertib | EXPERIMENTAL | 170 milligrams (mg) of prexasertib containing approximately 50 μCi \[¹⁴C\] prexasertib radiotracer administered intravenously (IV) as a 1 hour continuous IV infusion. |
| Prexasertib | EXPERIMENTAL | 105 milligrams per square meter (mg/m²) of prexasertib administered IV as a 1 hour continuous IV infusion once every 14 days (14 day cycles). Treatment may continue until discontinuation criteria are met. Treatment for this arm was administered after ¹⁴C administration (¹⁴C was administered during first phase of the study) |
| Part A: prexasertib + ralimetinib | EXPERIMENTAL | Cohort 1: 60 milligrams (mg) prexasertib (LY2606368) given intravenously (IV) and 100 mg ralimetinib given orally. Cohort 2: 60 mg prexasertib (LY2606368) given intravenously (IV) and 200 mg ralimetinib given orally. |
| Part B1: prexasertib + ralimetinib (colorectal cancer) | EXPERIMENTAL | 60 mg prexasertib (LY2696368) given IV and 200 mg ralimetinib given orally. Participants receive prexasertib IV on Days 1 and 15 and ralimetinib every 12 hours (Q12H) Days 1 and 14 of a 28 day cycle. |
| Prexasertib + Cisplatin + Radiation Therapy (Part A) | EXPERIMENTAL | Prexasertib administered intravenously (IV) every 14 days over an approximately 49-day treatment period. Cisplatin administered IV every 7 days over an approximately 49-day treatment period. Intensity modulated radiation therapy administered 5 days per week over an approximately 49-day treatment period. Participants may remain on treatment until completion of the treatment period. |
| Prexasertib + Cetuximab + Radiation Therapy (Part B) | EXPERIMENTAL | Prexasertib administered IV every 14 days over an approximately 56-day treatment period. Cetuximab administered IV every 7 days over an approximately 56-day treatment period. Intensity modulated radiation therapy administered 5 days per week over an approximately 56-day treatment period (starting at Week 2). Participants may remain on treatment until completion of the treatment period. |
| Prexasertib + Cisplatin (Part A) | EXPERIMENTAL | Part A: Prexasertib and cisplatin administered intravenously (IV) once every 21 days. Part A2: Prexasertib and cisplatin administered IV every 21 days; G-CSF administered subcutaneously (SC) starting approximately 24 hours after each prexasertib dose every 21 days. Part A3: Cisplatin administered IV on day one and prexasertib administered IV on day two once every 21 days. Part A Expansion: Part A, A2, and/or A3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met. |
| Prexasertib + Cetuximab (Part B) | EXPERIMENTAL | Part B: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days. Part B2: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days; G-CSF administered SC starting approximately 24 hours after each prexasertib dose every 14 days. Part B3: Cetuximab administered IV with prexasertib administered IV once every 14 days. Part B Expansion: Part B, B2 and/or B3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met. |
| Prexasertib + Pemetrexed (Part C) | EXPERIMENTAL | Part C: Pemetrexed administered IV on day one and prexasertib administered IV on day one and two every 21 days. Participants may remain on treatment until discontinuation criteria are met. |
| Prexasertib + 5-FU (Part D) | EXPERIMENTAL | Part D: Leucovorin administered IV on day one, 5-FU administered IV bolus on day one and by continuous IV on days one to three (46 hours), and prexasertib administered IV on day three every 14 days. Participants may remain on treatment until discontinuation criteria are met. |
| Prexasertib + LY3023414 (Part E) | EXPERIMENTAL | Part E: Prexasertib administered IV on day one and LY3023414 administered orally twice daily every 14 days. Part E will be expanded at the recommended dose in participants with advanced or metastatic cancer, participants with PIK3CA mutations (E2 expansion), or with advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer (E3 expansion). Participants may remain on treatment until discontinuation criteria are met. |
| Name | Type | Description |
|---|---|---|
| Prexasertib | DRUG | Administered IV |
| Cyclophosphamide | DRUG | IV |
| Gemcitabine | DRUG | IV |
| filgrastim | BIOLOGICAL | Given subcutaneously (SQ). Alternatively, pegfilgrastim may be given. |
| peg-filgrastim | BIOLOGICAL | Given subcutaneously (SQ). Alternatively, filgrastim may be given. |
| Olaparib | DRUG | Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor. |
| [¹⁴C]Prexasertib | DRUG | Administered IV Infusion |
| ralimetinib | DRUG | Administered orally |
| Cisplatin | DRUG | Administered IV |
| Cetuximab | DRUG | Administered IV |
| Intensity Modulated Radiation Therapy | RADIATION | - |
| G-CSF | DRUG | Administered SC |
| Pemetrexed | DRUG | Administered IV |
| Fluorouracil | DRUG | Administered IV |
| LY3023414 | DRUG | Administered PO |
| Leucovorin | DRUG | Administered IV |
Inclusion Criteria: * Women who have high-grade serous ovarian, primary peritoneal or fallopian tube cancer. * Cohorts 1 to 3: Have platinum-resistant disease and have documented test results assessing alterations in the BRCA1 and BRCA2 genes prior to receiving study treatment. * Cohort 1: Are BRCA...
Top 20 of 60 competitors
Prexasertib is an investigational small molecule cancer therapy developed by Eli Lilly and Company. It has been studied in advanced cancer, brain tumors, head and neck neoplasms, metastatic disease, and ovarian cancer. It is not approved and remains in clinical development, with completed trials in both adult and pediatric oncology populations.
Prexasertib targets CHEK1 and CHEK2, two checkpoint kinases involved in DNA damage response. It acts as an inhibitor of these enzymes. By blocking CHEK1 and CHEK2, the drug interferes with cancer cell DNA repair pathways. This mechanism underlies its study in tumors with DNA repair vulnerabilities, including biomarker-selected patient populations.
Prexasertib is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly conducted the clinical development program for the drug, including trials in ovarian cancer, medulloblastoma, and advanced solid tumors, both as a single agent and in combination regimens.
Prexasertib is in Phase 1 development overall, though one completed trial was listed as Phase 2. It is investigational and has not been approved by the FDA. All reported trials are completed, with no active studies, and the program has enrolled patients across adult and pediatric cancer indications.
Completed Prexasertib trials include NCT03414047 in platinum-resistant or refractory recurrent ovarian cancer, NCT04023669 in pediatric medulloblastoma combining the drug with cyclophosphamide or gemcitabine, NCT03057145 with olaparib in advanced solid tumors, and NCT02860780 with ralimetinib in advanced or metastatic cancer. All four studies have finished.
Yes, [¹⁴C]Prexasertib is an alternative name for Prexasertib. The bracketed carbon-14 label refers to a radiolabeled form used in research settings, while Prexasertib is the compound itself. Both names refer to the same CHEK1 and CHEK2 inhibitor developed by Eli Lilly and Company.