Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
HKI-272 · 4 trials · 6 indications
Defined as the percentage of patients achieving a complete response (CR) or partial response (PR) of Central Nervous System (CNS) lesions based on composite criteria, reported separately in Cohorts 1, 3A, 3B. For the volumetric criteria, an objective CR will be defined as the following: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks; no new lesions; stable or decreasing steroid dose; stable or improved neurological symptoms. An objective PR by volumetric criteria will be defined as the following: At least a 50% decrease in the sum volume of CNS target lesions, taking as reference the baseline sum volume sustained for at least 4 weeks; no new lesions; stable or decreasing steroid dose; stable or improved neurological symptoms.
Defined as the percentage of patients achieving a complete response (CR) or partial response (PR) of Central Nervous System (CNS) lesions based on RANO-BM criteria, reported separately in Cohorts 4A, 4B, and 4C. For the RANO-BM criteria, an objective CR will be defined as the following: Disappearance of all CNS target and non-target lesions sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. An objective PR by RANO-BM criteria will be defined as the following: At least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD sustained for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically.
Objective response rate as reported by Independent Assessment (radiographic review by independent radiologists) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | ACTIVE_COMPARATOR | Patients With Progressive Brain Metastases Intervention: HKI-272 (Neratinib)340 mg orally, once daily. |
| Cohort 2 | ACTIVE_COMPARATOR | Patients Who Are Candidates For Craniotomy. Intervention: HKI-272 (Neratinib) 240 mg orally, once daily. Surgical resection (biopsy). Neratinib concentrations from craniotomy specimen, CSF, plasma Neratinib. |
| Cohort 3a/3b | ACTIVE_COMPARATOR | Cohort 3a will be made up of participants with No Prior Lapatinib Treatment. They will receive Neratinib 240mg Orally daily and 750mg/m2 Capecitabine twice per day for 14 days followed by 7 days rest. Cohort 3b will be made of of participants with Prior Lapatinib Treatment. Cohort 3b participants will receive Neratinib 240mg Orally daily and 750mg/m2 Capecitabine twice per day for 14 days followed by 7 days rest. |
| Cohort 4a/4b/4c | ACTIVE_COMPARATOR | Cohort 4a will be made up of participants with previously untreated brain metastases. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks. Cohort 4b will be made up of participants with progressive brain metastases. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks. Cohort 4c will be made up of participants with progressive brain metastases and prior T-DM1. They will receive Neratinib 160mg Orally daily and T-DM1 3.6mg/kg IV every 3 weeks. |
| Prior Tarceva or Iressa With EGFR Mutation | EXPERIMENTAL | HKI-272 administered to patients whose disease has progressed following \> or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor with an EGFR mutation demonstrated at screening |
| Prior Tarceva or Iressa w/o EGFR Mutation | EXPERIMENTAL | HKI-272 administered to patients whose disease has progressed following \> or = 12 weeks of treatment with Tarceva or Iressa and who have a tumor without an EGFR mutation demonstrated at screening |
| No Prior EGFR Tyrosine Kinase Inhibitor Treatment | EXPERIMENTAL | HKI-272 administered to patients with no prior EGFR tyrosine kinase inhibitor treatment, adenocarcinoma, \< or = 20 pack-year smoking history, and current non-smoker (no requirement for EGFR mutation) |
| HKI-272 dose level 1 | EXPERIMENTAL | Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV. |
| HKI-272 dose level 2 | EXPERIMENTAL | Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV. |
| HKI-272 expanded MTD cohort, arm A | EXPERIMENTAL | Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV. |
| HKI-272 expanded MTD cohort, arm B | EXPERIMENTAL | Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m\^2 weekly IV. |
| Part 1 - dose level 1 (160 mg) | EXPERIMENTAL | All subjects receiving HKI-272 dose level 1 in combination with trastuzumab |
| Part 1 - dose level 2 (240 mg) | EXPERIMENTAL | All subjects receiving HKI-272 dose level 2 in combination with trastuzumab |
| Part 2 - expanded MTD cohort | EXPERIMENTAL | All subjects receiving HKI-272 in combination with trastuzumab |
| Name | Type | Description |
|---|---|---|
| HKI-272 | DRUG | 240 mg orally, once daily |
| Surgical Resection | PROCEDURE | Neratinib concentrations from craniotomy specimen, CSF, plasma Neratinib. |
| Capecitabine | DRUG | 750 mg/m2 orally, twice daily (1,500 mg/m2 daily) for 14 days followed by 7 days off |
| Ado-Trastuzumab Emtansine | DRUG | 3.6 mg/kg IV every 3 weeks |
| Paclitaxel | DRUG | - |
| trastuzumab | DRUG | trastuzumab 4 mg/kg IV as a loading dose followed by trastuzumab 2 mg/kg weekly thereafter |
Inclusion Criteria: * Patients (men or women) must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologi...
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HKI-272, also known as neratinib, is an investigational small molecule being studied for the treatment of advanced non-small cell lung cancer, advanced breast cancer, and breast cancer. It has been evaluated in clinical trials for these oncology indications, including in combination with other therapies.
HKI-272 is a small molecule that targets HER2, a protein involved in cell growth that is overexpressed in some cancers. By inhibiting HER2, HKI-272 aims to block signaling pathways that promote tumor growth, which is relevant in HER2-positive breast cancer and other solid tumors.
HKI-272 is being developed by Puma Biotechnology Inc, a biopharmaceutical company. The company's stock is traded under the ticker symbol PBYI on the stock market.
HKI-272 has completed Phase 1 and Phase 2 clinical trials. It is an investigational drug and has not been approved by the FDA. The completed trials include studies in advanced non-small cell lung cancer and advanced breast cancer.
HKI-272 has been studied in several completed clinical trials. These include NCT00266877 for advanced non-small cell lung cancer, NCT00398567 for advanced breast cancer in combination with trastuzumab, NCT00445458 for solid tumors and breast cancer with paclitaxel, and NCT01494662 for HER2-positive breast cancer with brain metastases.
Yes, HKI-272 is also known as neratinib. The drug has been referred to by both names in clinical research and development contexts, and they refer to the same investigational compound.