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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
582
240 mg administered orally, once daily with food, continuously in 28 day cycles
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
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
80mg/m\^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic Arizona
Phoenix, Arizona, United States
City of Hope
Duarte, California, United States
University of California, San Diego
La Jolla, California, United States
University of Southern California
Los Angeles, California, United States
University of California, Los Angeles
Los Angeles, California, United States
Stanford Cancer Center
Palo Alto, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Kaiser Permanente NoCal (STRATA)
Vallejo, California, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
...and 50 more locations
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.