Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
neratinib · 35 trials · 32 indications
Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months.
Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 48 months.
Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.
Percentage of participants with clinically assessed grade 3 or greater diarrhea reported within the first 2 cycles (each cycle is 21 days) of neratinib while using anti-diarrheal strategies. Reports of diarrhea will be graded according to NCI CTCAE version 4.0.
Percentage of participants who did not require loperamide during cancer treatment for at least 5 cycles will be reported.
The percentage of participants who discontinued all anti-diarrheal medications during cancer treatment for at least 5 cycles will be reported.
Percentage of participants with reported serious adverse events and adverse events of interest of any grade that have been determined to be related to the anti-diarrhea treatment will be reported by worst grade and associated toxicity.
The number of participants who experienced a dose hold of neratinib during the course of study therapy will be reported
The number of participants who discontinued neratinib earlier than expected during the course of study therapy will be reported
The number of participants whose dose was reduced at any time during the course of therapy will be reported
* Imaging for clinical benefit rate occurred at baseline (for an initial comparison scan) and every 2 cycles (28 day length) thereafter. * Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have had stable disease for at least 6 months.
* Imaging for clinical benefit rate occurred at baseline (for an initial comparison scan) and every 2 cycles (28 day length) thereafter. * Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have had stable disease for at least 6 months.
* Imaging for clinical benefit rate occurred at baseline (for an initial comparison scan) and every 2 cycles (28 day length) thereafter. * Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have had stable disease for at least 6 months.
* Imaging for clinical benefit rate occurred at baseline (for an initial comparison scan) and every 2 cycles (28 day length) thereafter. * Complete response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have had stable disease for at least 6 months.
The proportion of patients who discontinue the treatment with neratinib due to diarrhoea within this time period.
pCR is defined as the lack of all signs of invasive cancer in the breast removed during surgery
The primary endpoint is to describe the changes in colon pathology between the baseline colonoscopy and the second colonoscopy.
The primary objective of this study is to characterize the percentage of patients with Grade 3 or higher diarrhea in patients with early-stage HER2 overexpressed/amplified (HER2+) breast cancer treated with neratinib when administered with intensive loperamide prophylaxis, after prior treatment with trastuzumab. Grade 3: Increase of \>=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.
Progression Free Survival, Measured in Months, for Subjects Randomized. Investigator assessment. The time interval from the date of randomization until the earliest date of progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) or death due to any cause. For subjects without death or progression, censorship was at the last valid tumor assessment.
16 week progression-free survival (PFS) rate of neratinib in women with human epidermal growth factor receptor 2 (HER2) positive breast cancer, either with prior trastuzumab or no prior trastuzumab therapy, evaluated by independent assessment of tumor scans collected at baseline and then every 8 weeks.
The RP2D will be identified during the phase 1 dose escalation portion of the study using a modified 3+3 design and evaluated in a phase 1b dose expansion cohort of up to 12 patients with platinum-resistant ovarian cancer.
Phase 1b: To evaluate clinical benefit (≥4-month progression-free survival \[PFS\]) of niraparib and neratinib given at the RP2D to in patients with platinum-resistant ovarian cancer. To evaluate the clinical benefit, (defined as ≥4-month progression free survival (PFS), using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria in patients with platinum-resistant ovarian cancer.
RP2D for the combination of neratinib and sodium valproate that is less than or the same as the maximum tolerated dose (MTD).
The area under the plasma concentration-time curve, from time 0 to the last measurable nonzero concentration, as calculated by the linear trapezoidal method.
The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC(0-inf) is calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant.
Maximum observed concentration.
DLT was defined as 1. Grade 3 or 4 non-hematologic toxicity (exceptions listed below as a.-c.), a. Grade 3 asthenia was NOT considered to be a DLT UNLESS it lasted \>3 days. b. Grade 3 nausea or vomiting was NOT considered to be a DLT UNLESS the subject was already receiving optimal medical therapy. c. Grade 3 or 4 infection was NOT considered to be a DLT UNLESS it is associated with grade 3 or 4 neutropenia. 2. Grade 3 diarrhea that lasted \>2 days while the subject was on optimal medical therapy or that was associated with fever (greater than or equal 38.0 ºC) or grade 3 dehydration. 3. Grade 4 neutropenia lasting ≥3 days or grade 4 febrile neutropenia. 4. Grade 4 thrombocytopenia lasting ≥3 days or complicated with bleeding or requiring platelet transfusion. 5. Delayed recovery (to National Cancer Institute \[NCI\] grade 1 or less, or baseline) from any of the toxicities listed above (items 1-4), that was related to study drug, and that delayed the next dose by more than 3 weeks.
Six subjects will be initially enrolled (neratinib 240 mg/day; capecitabine 1500 mg/m²/day on days 1 through 14). AEs and DLTs will be assessed from the first dose of investigational product through day 21. Based on the DLT rate in these first 6 subjects, dose tolerability will be confirmed as follows: If ≤1 of the first 6 evaluable subjects experience a DLT by day 21, then this dose is considered tolerable, and enrollment will stop. If ≥3 of the first 6 evaluable subjects experience a DLT by day 21, this dose is considered intolerable. If 2 of the first 6 evaluable subjects experience a DLT by day 21, then an additional 4 subjects will be enrolled at the same dose level. If a total of 10 subjects are enrolled, then the tolerability will be confirmed as follows: If ≤3 of the total 10 subjects experience a DLT by day 21, then this dose will be considered tolerable. If ≥4 of the total 10 subjects experience a DLT by day 21, then the dose will be considered intolerable.
ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.
Number of participants experiencing DLT of neratinib in combination with vinorelbine in Japanese patients.
A DLT was defined as any dose-limiting Adverse Event related to neratinib + Temsirolimus as Grade 3 or higher nonhematologic toxicity (except neutropenia) or Grade 3 or higher diarrhea lasting \>2 days with optimal antidiarrheal therapy etc.
Identification of the daily neratinib high-dose MTD in combination with weekly temsirolimus.
Identification of the weekly temsirolimus high-dose MTD in combination with daily neratinib
A DLT was defined as any dose-limiting adverse event (AE) related to neratinib + TEMSR as follows: \[1\] Grade 3 or 4 nonhematologic toxicity (Grade 3 or 4 nausea, vomiting, hyperglycemia, hypophosphatemia, hypertriglyceridemia, or hypercholesterolemia was not considered a DLT unless the subject was already receiving optimal medical therapy). \[2\] Grade 3 or 4 diarrhea lasting \>2 days while subject was on optimal vigorous antidiarrheal therapy. \[3\] Grade 4 neutropenia lasting \>3 days or Grade 3 or 4 neutropenia of any duration with sepsis or a fever \>38.5C. \[4\] Platelet value less than or equal to 25,000/mm3 or bleeding requiring a platelet transfusion. \[5\] Delayed recovery from toxicity, which delayed rescheduled re-treatment for \>3 weeks. \[6\] Inability to maintain the original dose during the first 28 days of treatment (at least 21 doses of neratinib and 2 doses of TEMSR at the original specified dose) due to treatment-related toxicity.
Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
The maximum tolerated dose of neratinib, as determined by the incidence of DLTs, in combination with paclitaxel 80 mg/m\^2, in subjects with advanced solid tumors.
Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine 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.
MTD is defined as the prior dose level of the dose level which has \>=2 of 3 to 6 subjects that experience a neratinib-related DLT during 21 days from first dose date. A DLT is defined as any HKI-272-related nonhematologic grade 3 or any grade 4 AE according to the Common Terminology Criteria for Adverse Events version 3.0 except: Grade 3 nausea, vomiting, diarrhea, or rash unless subject was receiving appropriate medical therapy.
| Arm | Type | Description |
|---|---|---|
| neratinib plus capecitabine | EXPERIMENTAL | neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle. |
| lapatinib plus capecitabine | ACTIVE_COMPARATOR | lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle. |
| Neratinib | EXPERIMENTAL | 240 mg orally daily for one year |
| Placebo | PLACEBO_COMPARATOR | orally daily for one year |
| Adjuvant Neratinib, Crofelemer, Loperamide | EXPERIMENTAL | Participants will receive 240mg neratinib to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Participants will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks. Participants will also receive 125mg of prophylactic Crofelemer and 4 mg of prophylactic loperamide as needed in the first 2 cycles. |
| Adjuvant Neratinib, Loperamide | EXPERIMENTAL | Participants will receive 120 mg of neratinib on days 1-7 with subsequent increase in dose by 40 mg every 7 days until the full dose of 240 mg a day is reached within the first cycle (up to 240mg) to be taken continuously in 21-day cycles once a day for up to 55 weeks on study with no rest between cycles unless related to toxicity. Participants will receive Neratinib and may also be prescribed standard of care maintenance adjuvant trastuzumab (duration of maintenance trastuzumab is at the discretion of the treating physician), for up to 55 weeks. If applicable, after the completion of trastuzumab maintenance therapy (determined by treating physician), neratinib may continue as monotherapy to complete a maximum of 55 weeks. Participants will also receive 4 mg of prophylactic loperamide to be taken as needed. |
| Part I: Neratinib Only | EXPERIMENTAL | -Patients will receive neratinib PO daily on Days 1-28. Each cycle is 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Part II: Neratinib Only (ER-) | EXPERIMENTAL | -Patients will receive neratinib PO daily on Days 1-28. Each cycle is 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Part II: Neratinib + Fulvestrant (ER+, fulvestrant-naive) | EXPERIMENTAL | -Patients will receive neratinib PO daily on Days 1-28 and fulvestrant on Day 1 of each cycle (and C1D15). Each cycle is 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Part II: Neratinib + Fulvestrant (ER+. prior fulvestrant-tx) | EXPERIMENTAL | -Patients will receive neratinib PO daily on Days 1-28 and fulvestrant on Day 1 of each cycle (and C1D15). Each cycle is 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Crossover: Neratinib + Trastuzumab | EXPERIMENTAL | -If a participant experiences disease progression during Part I or Part II following neratinib, trastuzumab (or FDA approved biosimilar) may be added to the treatment regimen. Trastuzumab may be administered intravenously with a loading dose of 6 mg/kg then 4 mg/kg every 2 weeks. A cycle will be defined as 28 days. Patients will continue to receive neratinib PO daily on Days 1-28. Each cycle is 4 weeks. |
| Crossover: Neratinib + Fulvestrant + Trastuzumab | EXPERIMENTAL | -If a participant experiences disease progression during Part I or Part II following neratinib, trastuzumab (or FDA approved biosimilar) may be added to the treatment regimen. Trastuzumab may be administered intravenously with a loading dose of 6 mg/kg then 4 mg/kg every 2 weeks. A cycle will be defined as 28 days. Patients will receive neratinib PO daily on Days 1-28 and fulvestrant on Day 1 of each cycle (and C1D15). Each cycle is 4 weeks. |
| Arm A | EXPERIMENTAL | 1. Neratinib 240 mg (six 40mg tablets) orally once daily for 13 cycles (C) (1 C = 28 days), unless patient discontinues earlier. 2. Mandatory loperamide 4 mg (2 tablets/capsules) orally, 3 times a day (total 12 mg a day) starting Day (D) 1 of neratinib and for the first 14 days. Then, 4 mg (2 tablets/capsules) orally, 2 times a day (total 8 mg a day) until the end of C2 (D56); thereafter, loperamide will be administered PRN (without exceeding 16 mg per day). |
| Arm B | EXPERIMENTAL | 1. Neratinib 120 mg for Week 1 (C1D1 - C1D7), followed by 160 mg neratinib for Week 2 (C1D8 - C1D14), followed by 240 mg neratinib for Week 3 and thereafter for 13 cycles inclusive, until cycle 13 day 28 (unless patient discontinues earlier). 2. Loperamide to be administered PRN only (without exceeding 16 mg per day). |
| Arm C | EXPERIMENTAL | 1. Neratinib 240 mg (six 40-mg tablets) orally once daily for 13 C, unless patient discontinues earlier. 2. Mandatory loperamide 4 mg (2 tablets/capsules) orally, 3 times a day (total 12 mg a day) for the first 14 days. After the first 14 days, 4 mg (2 tablets/capsules) orally, 2 times a day (total 8 mg a day) to complete a total of 28 days. 3. Mandatory colesevelam 1,875 mg (three 625-mg capsules orally), 2 times a day for the first month (28 days). After day 28, any prophylaxis or treatment for diarrhoea could be administered PRN, if loperamide not to exceed 16 mg per day. |
| A | EXPERIMENTAL | Weeks 1-3\* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab \*Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization. |
| Temozolomide | ACTIVE_COMPARATOR | * Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Temozolomide will also be administered post radiation for up to 6 cycles (5 days/cycle) |
| Neratinib with Temozolomide | EXPERIMENTAL | * Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Neratinib will be taken post radiation at a daily oral pre-determine dose |
| QBS10072S | EXPERIMENTAL | Daily Radiation for a maximum of 49 days. QBS10072S will be administered on Day 1 of Radiation Treatment QBS10072S will be administered post- radiation for up to 6 cycles |
| Abemaciclib with Temozolomide | EXPERIMENTAL | * Daily Radiation for a maximum of 49 days. * Temozolomide will be administered orally on a daily dosing schedule during radiation * Temozolomide will be administered approximately 2-3 hours before each session of radiotherapy * Abemaciclib will be taken post radiation at a twice daily oral pre-determined dose |
| CC-115 | EXPERIMENTAL | * Twice daily oral dosing of CC-115 * Daily Radiation for a maximum of 49 days * CC115 will also be taken twice daily post radiation |
| Loperamide | EXPERIMENTAL | 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed. |
| Budesonide and Loperamide | EXPERIMENTAL | 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter. |
| Colestipol and Loperamide | EXPERIMENTAL | 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter. |
| Colestipol with Loperamide as needed | EXPERIMENTAL | 240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed. |
| Neratinib Dose Escalation 1 | EXPERIMENTAL | 120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed. |
| Neratinib Dose Escalation 2 | EXPERIMENTAL | 160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only. |
| neratinib monotherapy | EXPERIMENTAL | 240 mg once daily with food, continuously in 21 day cycles |
| neratinib plus temsirolimus | EXPERIMENTAL | 240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus |
| neratinib plus paclitaxel | EXPERIMENTAL | - |
| trastuzumab plus paclitaxel | ACTIVE_COMPARATOR | - |
| Neratinib 240 mg, with prior trastuzumab | EXPERIMENTAL | Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen. |
| Neratinib 240 mg, no prior trastuzumab | EXPERIMENTAL | Neratinib administered with 80 mg capsules and 40 mg coated tablets taken orally in prescribed dose of 240 mg daily, as long as tolerated and disease does not worsen. |
| Dose Level -1 | EXPERIMENTAL | Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles. |
| Dose Level 1 | EXPERIMENTAL | Neratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 2 | EXPERIMENTAL | Neratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 3 | EXPERIMENTAL | Neratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 4 | EXPERIMENTAL | Neratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles. |
| Phase 1b: Platinum Resistant Expansion Cohort | EXPERIMENTAL | This portion of the study provides for cohort expansion to observe for 4 month or greater progression-free survival in patients with platinum resistant ovarian cancer treated at the recommended phase 2 dose (RP2D) determined in Phase I. |
| Neratinib + Divalproex Sodium - Dose Escalation Cohort | EXPERIMENTAL | Neratinib by mouth (PO) once daily + Divalproex Sodium (Valproate) by mouth (PO) twice daily on days 1-28 of each course. |
| Colon | EXPERIMENTAL | Colon Cancer (RAS-mutated) - Phase II dose expansion at recommended phase II dose (RP2D) |
| Glioblastoma (GBM) | EXPERIMENTAL | Glioblastoma with a RAS-mutation or EGFR alteration at RP2D |
| Ocular Melanoma (OM) | EXPERIMENTAL | Phase II dose expansion at RP2D |
| Other Cancer | EXPERIMENTAL | "Other Cancer" (RAS-mutated) at RP2D |
| Pancreatic Cancer | EXPERIMENTAL | RAS-mutated pancreatic cancer at RP2D |
| Treatment A (Period 1) and Treatment B (Period 2) | EXPERIMENTAL | Treatment A (240mg Neratinib x1) Treatment B (30mg Lansoprazole X 7 days + 240mg Neratinib x1) |
| Neratinib + Capecitabine | EXPERIMENTAL | Neratinib + Capecitabine |
| Temsirolimus plus Neratinib | EXPERIMENTAL | This is an open-label, single arm, dose-escalation phase I-II study to determine the maximum tolerated dose (MTD) of temsirolimus with daily neratinib, and to determine the safety and efficacy of this combination when given to patients with advanced breast carcinoma. Patients with trastuzumab-refractory HER2-amplified disease or triple negative disease will be enrolled in both phases of this clinical trial. |
| Neratinib and Vinorelbine | EXPERIMENTAL | Neratinib: 240 mg administered daily by mouth continuously, Vinorelbine: 25 mg/m\^2 administered IV on Day 1 and 8 of 21 day cycle |
| 1 | EXPERIMENTAL | Neratinib alone |
| 2 | EXPERIMENTAL | Neratinib plus rifampin |
| Neratinib and Temsirolimus (Dose level 1) | EXPERIMENTAL | Neratinib 120 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 2) | EXPERIMENTAL | Neratinib 120 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 3) | EXPERIMENTAL | Neratinib 120 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 4) | EXPERIMENTAL | Neratinib 120 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 5) | EXPERIMENTAL | Neratinib 160 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 6) | EXPERIMENTAL | Neratinib 160 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 7) | EXPERIMENTAL | Neratinib 160 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 8) | EXPERIMENTAL | Neratinib 160 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 9) | EXPERIMENTAL | Neratinib 200 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 10) | EXPERIMENTAL | Neratinib 200 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 11) | EXPERIMENTAL | Neratinib 200 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| Neratinib and Temsirolimus (Dose level 12) | EXPERIMENTAL | Neratinib 240 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen |
| 3 | EXPERIMENTAL | 80-mg capsule |
| Neratinib and Capecitabine (Dose Level 1) | EXPERIMENTAL | Neratinib 160 mg and Capecitabine 1500 mg/m\^2 |
| Neratinib and Capecitabine (Dose Group 2) | EXPERIMENTAL | Neratinib 240 mg and Capecitabine 1500 mg/m\^2 |
| Neratinib and Capecitabine (Dose Group 3) | EXPERIMENTAL | Neratinib 240 mg and Capecitabine 2000 mg/m\^2 |
| Neratinib and Capecitabine (Dose Group 4) | EXPERIMENTAL | Neratinib 200 mg and Capecitabine 2000 mg/m\^2 |
| Neratinib and Capecitabine (Dose Group 5) | EXPERIMENTAL | Neratinib 160 mg and Capecitabine 2000 mg/m\^2 |
| Neratinib and Capecitabine MTD (Dose Group 6) | EXPERIMENTAL | Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib |
| Neratinib and Capecitabine MTD (Dose Group 7) | EXPERIMENTAL | Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib |
| Nera 160 + Pac | EXPERIMENTAL | Neratinib 160 mg + Paclitaxel 80 mg/m\^2 |
| Nera 240 + Pac | EXPERIMENTAL | Neratinib 240 mg + Paclitaxel 80 mg/m\^2 |
| QD | EXPERIMENTAL | Once daily |
| BID | EXPERIMENTAL | Twice daily |
| neratinib 160 mg + vinorelbine | EXPERIMENTAL | neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine | EXPERIMENTAL | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine, No Prior Lapatinib | EXPERIMENTAL | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle |
| neratinib 240 mg + vinorelbine, Prior Lapatinib | EXPERIMENTAL | neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle |
| Neratinib 80 mg | EXPERIMENTAL | - |
| Neratinib 160 mg | EXPERIMENTAL | - |
| Neratinib 240 mg | EXPERIMENTAL | - |
| Neratinib 320 mg | EXPERIMENTAL | - |
| Neratinib 40 mg | EXPERIMENTAL | - |
| Neratinib 120 mg | EXPERIMENTAL | - |
| Neratinib 180 mg | EXPERIMENTAL | - |
| Neratinib 400 mg | EXPERIMENTAL | - |
| Neratinib 320 mg MTD | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| neratinib | DRUG | - |
| capecitabine | DRUG | - |
| lapatinib | DRUG | - |
| placebo | OTHER | - |
| Trastuzumab | BIOLOGICAL | Given Intravenously (IV) |
| Loperamide | DRUG | Given PO |
| Crofelemer | DRUG | Given PO |
| Diphenoxylate/Atropine | DRUG | Allowed for participants experiencing refractory diarrhea |
| Fulvestrant | DRUG | - |
| Tumor biopsy | PROCEDURE | -Optional at baseline and disease progression |
| Research blood sample | PROCEDURE | -Baseline, cycle 1 day 15, cycle 2 day 1, cycle 3 day 1, day 1 of each odd cycle, end of treatment (progression) |
| Colesevelam | DRUG | Colesevelam capsules orally, 2 times a day for the first month (28 days). |
| Letrozole (L) or Anastrozole (A) | DRUG | L: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)\* |
| Temozolomide | DRUG | Temzolomide capsules |
| QBS10072S | DRUG | QBS10072S administered intravenously |
| Abemaciclib | DRUG | Abemaciclib tablets |
| CC-115 | DRUG | CC-115 tablets |
| Colestipol | DRUG | 2 g twice daily with or without food for one 28 day cycle |
| Budesonide | DRUG | 9 mg extended release tablets once daily with or without food for 28 days |
| temsirolimus | DRUG | - |
| Paclitaxel | DRUG | Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. |
| Neratinib 160 mg | DRUG | Escalating doses to determine recommended phase 2 dose (RP2D) |
| Neratinib 200 mg | DRUG | Determined RP2D dose |
| Neratinib 240 mg | DRUG | Escalating doses to determine recommended phase 2 dose (RP2D) |
| Niraparib 100 mg | DRUG | Escalating doses to determine recommended phase 2 dose (RP2D) |
| Niraparib 200 mg | DRUG | Escalating doses to determine recommended phase 2 dose (RP2D) |
| Niraparib 300 mg | DRUG | Phase 1: Escalating doses to determine recommended phase 2 dose (RP2D) |
| Niraparib at RP2D | DRUG | Phase 1b: Determined dose |
| Neratinib at RP2D | DRUG | Phase 1b: Determined dose |
| Divalproex Sodium | DRUG | Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion). |
| Lansoprazole | DRUG | - |
| Vinorelbine | DRUG | - |
| Digoxin | DRUG | - |
| Neratinib (HKI-272) | DRUG | Neratinib 40-mg oral tablets. SINGLE DOSE of 120-mg (3 x 40-mg tablets) |
| Moxifloxacin | DRUG | - |
Inclusion Criteria: * Aged ≥18 years at signing of informed consent. * Histologically confirmed MBC, current stage IV. * Documented HER2 overexpression or gene-amplified tumor immunohistochemistry 3+ or 2+, with confirmatory fluorescence in situ hybridization (FISH) +. * Prior treatment with at lea...
Top 20 of 97 competitors