A Phase 2 interventional study of Neratinib and Fulvestrant in Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations, sponsored by Puma Biotechnology, Inc.. Terminated at 60 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.
Sponsored by Puma Biotechnology, Inc. · Phase 2, Interventional, and Treatment
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors. The study has a basket design and includes several cohorts, either defined by an actionable somatic mutation or by actionable mutation and tumor histology, including HER2 mutant breast, HER2 mutant cervical, HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers.
The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 days after the last dose of neratinib and a survival follow-up period.
10,818 studies on the registry are indexed under Neoplasms; 2,324 are open to participants now.
This study's enrollment of 582 is above the median of 60 across 7,703 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Puma Biotechnology, Inc. is the lead sponsor of 38 studies on the registry; 3 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations. Cohorts closed to enrollment in prior amendments: HER2 mutant cancers including bladder/urinary, colorectal, endometrial, breast HR-positive, TNBC HR-negative, lung, gastroesophageal, biliary, and ovarian; HER3 mutant solid tumor NOS; HER4 mutant solid tumor NOS; fibrolamellar carcinoma and EGFR brain.
Drug: Neratinib
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.
Drug: Neratinib · Drug: Trastuzumab
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
Drug: Neratinib · Drug: Fulvestrant · Drug: Trastuzumab
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
Drug: Neratinib · Drug: Fulvestrant · Drug: Trastuzumab
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
Drug: Neratinib · Drug: Paclitaxel
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
Drug: Neratinib · Drug: Fulvestrant
240 mg administered orally, once daily with food, continuously in 28 day cycles
Also known as: Nerlynx
500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle
Also known as: Faslodex
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Also known as: Herceptin
80mg/m\^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
Also known as: Taxol
Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort)
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (cervical cancer cohort). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts)
Percentage of participants who achieve CR or PR per Response Evaluation Criteria in Sold Tumors Criteria (RECIST) v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts), per RECIST (if assessed) or PERCIST. RECISTv1.1 for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR PERCISTv1.0: Complete Metabolic Response - Complete resolution of 18F-FDG uptake within measurable target lesion so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels Partial Metabolic Response - Reduction of minimum of 30% in target measurable tumour 18F-FDG SULpeak. Absolute drop in SUL must be at least 0.8 SUL units, as well. No new lesions. Positive Metabolic Response - Participants having either "Complete Metabolic Response" or "Part
Time frame: From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks
Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort)
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts)
Percentage of participants who achieve CR or PR per RECIST v1.1, or metabolic complete response via PERCIST v1.0. For RECIST, A complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met. PERCIST criteria were used for patients without RECIST assessments.
Time frame: From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months.
Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.
Time frame: From first response to first disease progression or death, assessed up to 58 months
Duration of Response (DOR) by Investigator Review (All Cohorts)
Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.
Time frame: From first response to first disease progression or death, assessed up to 58 months
Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
Time frame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months
Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts)
Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
Time frame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months
Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.
Time frame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months
Progression-Free Survival (PFS) by Investigator Review (All Cohorts)
Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.
Time frame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months
Number of Participants With Treatment-Emergent Adverse Events
The safety of neratinib in patients as measured by the incidence of treatment-emergent adverse events (TEAE), including serious adverse events (SAEs), in study participants. TEAEs are any adverse event that occurred on or after first dose of investigational product and up to 28 days after the last dose
Time frame: From first dose through 28 days after the last dose, assessed up to 75 months.
| Milestone | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab |
|---|---|---|---|---|---|---|---|
| Started | 318 | 45 | 23 | 92 | 90 | 7 | 7 |
| Treated | 317 | 45 | 22 | 92 | 90 | 7 | 7 |
| Completed | 231 | 31 | 14 | 70 | 32 | 2 | 0 |
| Not completed | 87 | 14 | 9 | 22 | 58 | 5 | 7 |
| Withdrew: Withdrawal by subject | 23 | 3 | 3 | 5 | 6 | 0 | 1 |
| Withdrew: Physician decision | 1 | 0 | 0 | 0 | 2 | 0 | 0 |
| Withdrew: Lost to follow-up | 18 | 3 | 0 | 5 | 3 | 0 | 0 |
| Withdrew: Protocol violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Other, disease progression | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Discontinuation of study by sponsor | 41 | 7 | 5 | 12 | 46 | 5 | 6 |
| Withdrew: Not treated | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
| percentage of participants | Breast HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast HR+ w. Prior CDK4/6i (Fulvestrant) | Breast HR+ With Prior CDK4/6i (Fulvestrant + Trastuzumab) |
|---|---|---|---|
| Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) | 40.7 | 0 | 14.3 |
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (cervical cancer cohort). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
| percentage of participants | Cervical (Neratinib) |
|---|---|
| Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort) | 18.2 |
Percentage of participants who achieve CR or PR per Response Evaluation Criteria in Sold Tumors Criteria (RECIST) v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts), per RECIST (if assessed) or PERCIST. RECISTv1.1 for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR PERCISTv1.0: Complete Metabolic Response - Complete resolution of 18F-FDG uptake within measurable target lesion so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels Partial Metabolic Response - Reduction of minimum of 30% in target measurable tumour 18F-FDG SULpeak. Absolute drop in SUL must be at least 0.8 SUL units, as well. No new lesions. Positive Metabolic Response - Participants having either "Complete Metabolic Response" or "Part
| percentage of participant | Breast Cancer (Neratinib) | Breast Cancer HR+ (Neratinib + Fulvestrant) | Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR- (Neratinib + Trastuzumab) | Lung Cancer HER2 Mutant (Neratinib) | Lung Cancer HER2 Mutant (Neratinib + Trastuzumab) | Lung Cancer EGFR Mutant Exon 18 (Neratinib) | Biliary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel) | Brain Cancer (Neratinib) | Colorectal Cancer (Neratinib) | Colorectal Cancer (Neratinib + Trastuzumab) | Endometrial Cancer (Neratinib) | Ovarian Cancer (Neratinib) | Salivary Gland Cancer (Neratinib) | Gastroesophageal Cancer (Neratinib) | Fibrolamellar Carcinoma (FLC) (Neratinib) | HER2 NOS Cancer (Neratinib) | HER3 NOS Cancer (Neratinib) | HER4 NOS Cancer (Neratinib) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts) | 36.1 | 42.2 | 48.4 | 33.3 | 3.8 | 15.4 | 19.4 | 12.0 | 0 | 13.6 | 0 | 0 | 5.3 | 0 | 0 | 36.4 | 0 | 0 | 4.8 | 0 | 0 |
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
| percentage of participants | Breast HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast HR+ w. Prior CDK4/6i (Fulvestrant) | Breast HR+ With Prior CDK4/6i (Fulvestrant + Trastuzumab) |
|---|---|---|---|
| Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort) | 30.5 | 0 | 0 |
Percentage of participants who achieve CR or PR per RECIST v1.1, or metabolic complete response via PERCIST v1.0. For RECIST, A complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met. PERCIST criteria were used for patients without RECIST assessments.
| percentage of participant | Breast Cancer (Neratinib) | Breast Cancer HR+ (Neratinib + Fulvestrant) | Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR- (Neratinib + Trastuzumab) | Lung Cancer HER2 Mutant (Neratinib) | Lung Cancer HER2 Mutant (Neratinib + Trastuzumab) | Lung Cancer EGFR Mutant Exon 18 (Neratinib) | Biliary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel) | Brain Cancer (Neratinib) | Colorectal Cancer (Neratinib) | Colorectal Cancer (Neratinib + Trastuzumab) | Endometrial Cancer (Neratinib) | Ovarian Cancer (Neratinib) | Salivary Gland Cancer (Neratinib) | Gastroesophageal Cancer (Neratinib) | Fibrolamellar Carcinoma (FLC) (Neratinib) | HER2 NOS Cancer (Neratinib) | HER3 NOS Cancer (Neratinib) | HER4 NOS Cancer (Neratinib) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts) | 25.0 | 28.9 | 35.5 | 33.3 | 3.8 | 9.6 | 32.3 | 16.0 | 0 | 13.6 | 2.6 | 0 | 5.3 | 0 | 0 | 9.1 | 0 | 0 | 2.4 | 0 | 0 |
Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.
| month | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) |
|---|---|---|---|
| Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) | 13.14 (6.41 to NA) | — | NA (NA to NA) |
Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.
| month | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) | Breast Cancer (Neratinib) | Breast Cancer HR+ (Neratinib + Fulvestrant) | Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR- (Neratinib + Trastuzumab) | Cervical Cancer (Neratinib) | Lung Cancer HER2 Mutant (Neratinib) | Lung Cancer HER2 Mutant (Neratinib + Trastuzumab) | Lung Cancer EGFR Mutant Exon 18 (Neratinib) | Biliary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel) | Brain Cancer (Neratinib) | Colorectal Cancer (Neratinib) | Colorectal Cancer (Neratinib + Trastuzumab) | Endometrial Cancer (Neratinib) | Ovarian Cancer (Neratinib) | Salivary Gland Cancer (Neratinib) | Gastroesophageal Cancer (Neratinib) | Fibrolamellar Carcinoma (FLC) (Neratinib) | HER2 NOS Cancer (Neratinib) | HER3 NOS Cancer (Neratinib) | HER4 NOS Cancer (Neratinib) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Duration of Response (DOR) by Investigator Review (All Cohorts) | 14.4 (7.8 to 18.6) | — | — | 4.76 (3.71 to 16.62) | 9.23 (5.49 to 38.97) | 9.17 (4.14 to NA) | 7.28 (4.17 to NA) | 7.62 (5.55 to 12.25) | 9.23 (NA to NA) | 6.80 (4.17 to NA) | 22.24 (4.01 to 30.03) | 3.75 (2.99 to 4.67) | — | 7.20 (2.76 to 7.59) | 19.94 (NA to NA) | — | 12.19 (NA to NA) | — | — | NA (NA to NA) | — | — | 3.71 (NA to NA) | — | — |
Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
| percentage of participant | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) |
|---|---|---|---|
| Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) | 49.2 | 0 | 14.3 |
Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
| percentage of participant | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) | Breast Cancer (Neratinib) | Breast Cancer HR+ (Neratinib + Fulvestrant) | Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR- (Neratinib + Trastuzumab) | Cervical Cancer (Neratinib) | Lung Cancer HER2 Mutant (Neratinib) | Lung Cancer HER2 Mutant (Neratinib + Trastuzumab) | Lung Cancer EGFR Mutant Exon 18 (Neratinib) | Biliary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel) | Brain Cancer (Neratinib) | Colorectal Cancer (Neratinib) | Colorectal Cancer (Neratinib + Trastuzumab) | Endometrial Cancer (Neratinib) | Ovarian Cancer (Neratinib) | Salivary Gland Cancer (Neratinib) | Gastroesophageal Cancer (Neratinib) | Fibrolamellar Carcinoma (FLC) (Neratinib) | HER2 NOS Cancer (Neratinib) | HER3 NOS Cancer (Neratinib) | HER4 NOS Cancer (Neratinib) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts) | 54.2 | 0 | 0 | 33.3 | 42.2 | 54.8 | 42.9 | 45.5 | 38.5 | 30.8 | 48.4 | 24.0 | 18.8 | 31.8 | 10.5 | 8.3 | 21.1 | 14.3 | 20.0 | 54.5 | 0 | 13.3 | 19.0 | 6.3 | 0 |
Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.
| month | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) |
|---|---|---|---|
| Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) | 8.11 (6.01 to 16.39) | 2.27 (1.61 to NA) | 4.11 (1.87 to 4.11) |
Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.
| month | Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant) | Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab) | Breast Cancer (Neratinib) | Breast Cancer HR+ (Neratinib + Fulvestrant) | Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab) | Breast Cancer HR- (Neratinib + Trastuzumab) | Cervical Cancer (Neratinib) | Lung Cancer HER2 Mutant (Neratinib) | Lung Cancer HER2 Mutant (Neratinib + Trastuzumab) | Lung Cancer EGFR Mutant Exon 18 (Neratinib) | Biliary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib) | Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel) | Brain Cancer (Neratinib) | Colorectal Cancer (Neratinib) | Colorectal Cancer (Neratinib + Trastuzumab) | Endometrial Cancer (Neratinib) | Ovarian Cancer (Neratinib) | Salivary Gland Cancer (Neratinib) | Gastroesophageal Cancer (Neratinib) | Fibrolamellar Carcinoma (FLC) (Neratinib) | HER2 NOS Cancer (Neratinib) | HER3 NOS Cancer (Neratinib) | HER4 NOS Cancer (Neratinib) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Progression-Free Survival (PFS) by Investigator Review (All Cohorts) | 8.3 (6.0 to 12.7) | 4.1 (1.6 to 4.1) | 3.9 (1.9 to 4.1) | 3.48 (1.94 to 3.88) | 5.36 (3.71 to 9.23) | 8.21 (4.07 to 11.01) | 6.24 (2.10 to 10.25) | 5.09 (1.74 to 7.23) | 4.17 (1.87 to 8.80) | 4.01 (2.10 to 4.57) | 5.75 (2.27 to 9.23) | 2.76 (1.05 to 3.75) | 1.77 (1.68 to 3.55) | 3.75 (1.87 to 5.62) | 1.81 (1.02 to 2.69) | 1.71 (1.45 to 1.87) | 2.04 (1.81 to 3.48) | 1.87 (1.61 to 6.87) | 2.37 (1.48 to 7.36) | 5.32 (1.81 to 9.26) | 1.74 (0.82 to 2.23) | 3.58 (1.84 to 3.71) | 1.84 (1.74 to 2.07) | 1.69 (1.41 to 2.04) | 1.71 (1.12 to 1.74) |
The safety of neratinib in patients as measured by the incidence of treatment-emergent adverse events (TEAE), including serious adverse events (SAEs), in study participants. TEAEs are any adverse event that occurred on or after first dose of investigational product and up to 28 days after the last dose
| Participants | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab |
|---|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event | 313 | 45 | 21 | 92 | 89 | 7 | 7 |
| Any treatment-emergent serious adverse event | 144 | 12 | 13 | 45 | 28 | 5 | 0 |
Collected over All events from day 1 of study drug through 28 days after last dose are included, up to 75 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Neratinib | 231/317 (72.9%) | 144/317 (45.4%) | 304/317 (95.9%) |
| Neratinib + Fulvestrant | 31/45 (68.9%) | 12/45 (26.7%) | 45/45 (100%) |
| Neratinib + Paclitaxel | 14/22 (63.6%) | 13/22 (59.1%) | 20/22 (90.9%) |
| Neratinib + Trastuzumab | 71/92 (77.2%) | 45/92 (48.9%) | 92/92 (100%) |
| Neratinib + Fulvestrant + Trastuzumab | 32/90 (35.6%) | 28/90 (31.1%) | 89/90 (98.9%) |
| Fulvestrant | 2/7 (28.6%) | 5/7 (71.4%) | 7/7 (100%) |
| Fulvestrant + Trastuzumab | 0/7 (0%) | 0/7 (0%) | 7/7 (100%) |
| Event | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab |
|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 30/317 | 1/45 | 6/22 | 12/92 | 6/90 | 3/7 | 0/7 |
| Acute kidney injuryRenal and urinary disorders | 5/317 | 0/45 | 4/22 | 6/92 | 4/90 | 0/7 | 0/7 |
| Abdominal painGastrointestinal disorders | 17/317 | 0/45 | 3/22 | 3/92 | 0/90 | 1/7 | 0/7 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 1/317 | 0/45 | 0/22 | 0/92 | 0/90 | 1/7 | 0/7 |
| AstheniaGeneral disorders | 2/317 | 0/45 | 0/22 | 2/92 | 0/90 | 1/7 | 0/7 |
| PyrexiaGeneral disorders | 7/317 | 0/45 | 0/22 | 3/92 | 1/90 | 1/7 | 0/7 |
| Bone painMusculoskeletal and connective tissue disorders | 0/317 | 0/45 | 0/22 | 1/92 | 0/90 | 1/7 | 0/7 |
| AphasiaNervous system disorders | 0/317 | 0/45 | 0/22 | 0/92 | 0/90 | 1/7 | 0/7 |
| DisorientationPsychiatric disorders | 0/317 | 0/45 | 0/22 | 0/92 | 0/90 | 1/7 | 0/7 |
| Intestinal obstructionGastrointestinal disorders | 2/317 | 0/45 | 2/22 | 1/92 | 2/90 | 0/7 | 0/7 |
| Event | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab |
|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 211/317 | 39/45 | 16/22 | 74/92 | 82/90 | 6/7 | 6/7 |
| NauseaGastrointestinal disorders | 133/317 | 19/45 | 11/22 | 43/92 | 59/90 | 3/7 | 3/7 |
| VomitingGastrointestinal disorders | 105/317 | 10/45 | 10/22 | 42/92 | 44/90 | 1/7 | 2/7 |
| FatigueGeneral disorders | 98/317 | 12/45 | 10/22 | 33/92 | 33/90 | 2/7 | 1/7 |
| ConstipationGastrointestinal disorders | 111/317 | 17/45 | 7/22 | 28/92 | 34/90 | 2/7 | 3/7 |
| Decreased appetiteMetabolism and nutrition disorders | 84/317 | 13/45 | 6/22 | 25/92 | 34/90 | 3/7 | 1/7 |
| Abdominal painGastrointestinal disorders | 60/317 | 8/45 | 5/22 | 12/92 | 26/90 | 0/7 | 1/7 |
| HyponatraemiaMetabolism and nutrition disorders | 9/317 | 2/45 | 2/22 | 4/92 | 4/90 | 0/7 | 2/7 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 23/317 | 7/45 | 5/22 | 12/92 | 11/90 | 1/7 | 2/7 |
| HeadacheNervous system disorders | 30/317 | 8/45 | 0/22 | 6/92 | 17/90 | 2/7 | 1/7 |
| Age, Categorical(Participants) | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 201 | 28 | 4 | 57 | 59 | 6 | 3 | 358 |
| >=65 years | 116 | 17 | 18 | 35 | 31 | 1 | 4 | 222 |
| Age, Continuous(years) | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 59.4 ± 13.1 | 60.6 ± 11.5 | 69.4 ± 9.4 | 60.4 ± 11.1 | 59.2 ± 11.6 | 58.3 ± 11.2 | 62.0 ± 12.4 | 60.0 ± 12.4 |
| Sex: Female, Male(Participants) | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 188 | 45 | 5 | 58 | 89 | 7 | 7 | 399 |
| Male | 129 | 0 | 17 | 34 | 1 | 0 | 0 | 181 |
| Race/Ethnicity, Customized(Participants) | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| Race — White | 255 | 38 | 21 | 70 | 77 | 7 | 5 | 473 |
| Race — Asian | 18 | 2 | 0 | 7 | 1 | 0 | 0 | 28 |
| Race — Black or African American | 16 | 1 | 0 | 4 | 4 | 0 | 1 | 26 |
| Race — American Indian or Alaska Native | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 3 |
| Race — Other | 6 | 1 | 0 | 2 | 0 | 0 | 0 | 9 |
| Race — Unknown | 7 | 1 | 0 | 4 | 1 | 0 | 0 | 13 |
| Race — Not Reported | 13 | 2 | 1 | 5 | 7 | 0 | 0 | 28 |
| Tumor type(Participants) | Neratinib | Neratinib + Fulvestrant | Neratinib + Paclitaxel | Neratinib + Trastuzumab | Neratinib + Fulvestrant + Trastuzumab | Fulvestrant | Fulvestrant + Trastuzumab | Total |
|---|---|---|---|---|---|---|---|---|
| Breast cancer HR+ or HR- | 36 | 0 | 0 | 0 | 0 | 0 | 0 | 36 |
| Breast cancer HR+ | 0 | 45 | 0 | 0 | 31 | 0 | 0 | 76 |
| Breast cancer HR+, prior CDK46 inhibitors | 0 | 0 | 0 | 0 | 59 | 7 | 7 | 73 |
| Breast cancer HR- | 0 | 0 | 0 | 21 | 0 | 0 | 0 | 21 |
| Lung Her2 mutant cancer | 26 | 0 | 0 | 52 | 0 | 0 | 0 | 78 |
| Lung EGFR mutant exon 18 cancer | 31 | 0 | 0 | 0 | 0 | 0 | 0 | 31 |
| Biliary tract cancer | 25 | 0 | 0 | 0 | 0 | 0 | 0 | 25 |
| Cervical cancer | 22 | 0 | 0 | 0 | 0 | 0 | 0 | 22 |
| Bladder/Urinary Tract cancer | 16 | 0 | 22 | 0 | 0 | 0 | 0 | 38 |
| Brain EGFR mutant cancer | 38 | 0 | 0 | 0 | 0 | 0 | 0 | 38 |
| Colorectal cancer | 12 | 0 | 0 | 19 | 0 | 0 | 0 | 31 |
| Salivary gland cancer | 11 | 0 | 0 | 0 | 0 | 0 | 0 | 11 |
| Endometrial cancer | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Fibrolamellar carcinoma (FLC) | 15 | 0 | 0 | 0 | 0 | 0 | 0 | 15 |
| Gastroesophageal cancer | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Ovarian cancer | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 10 |
| HER2 NOS cancer | 42 | 0 | 0 | 0 | 0 | 0 | 0 | 42 |
| HER3 NOS cancer | 16 | 0 | 0 | 0 | 0 | 0 | 0 | 16 |
| HER4 NOS cancer | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.
Access criteria: Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest. Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.
Data sharing details ↗ · pumabiotechnology.com
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Studies of the drug tested here: Neratinib