Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations (SUMMIT)
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| ClinicalTrials.gov Identifier: NCT01953926 |
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Recruitment Status :
Terminated
(The study was terminated to align with the sponsor's current development plans for neratinib. The decision was not based on any new efficacy or safety data for neratinib.)
First Posted : October 1, 2013
Results First Posted : March 12, 2024
Last Update Posted : March 12, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations | Drug: Neratinib Drug: Fulvestrant Drug: Trastuzumab Drug: Paclitaxel | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 582 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations |
| Actual Study Start Date : | September 30, 2013 |
| Actual Primary Completion Date : | January 2, 2023 |
| Actual Study Completion Date : | January 2, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Neratinib monotherapy
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
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx |
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Experimental: Neratinib and Trastuzumab
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
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx Drug: Trastuzumab Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Other Name: Herceptin |
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Experimental: Neratinib, Fulvestrant and Trastuzumab (Randomized)
Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
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Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx Drug: Fulvestrant 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
Other Name: Faslodex Drug: Trastuzumab Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Other Name: Herceptin |
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Experimental: Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
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Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx Drug: Fulvestrant 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
Other Name: Faslodex Drug: Trastuzumab Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Other Name: Herceptin |
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Experimental: Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
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Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx Drug: Paclitaxel 80mg/m^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
Other Name: Taxol |
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Experimental: Neratinib and Fulvestrant
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
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Drug: Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Other Name: Nerlynx Drug: Fulvestrant 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
Other Name: Faslodex |
- Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) [ Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months ]
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
- Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort) [ Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months ]
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
- Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts) [ Time Frame: From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks ]
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
- Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort) [ Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months ]
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
- Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts) [ Time Frame: From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months. ]
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.
- Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) [ Time Frame: From first response to first disease progression or death, assessed up to 58 months ]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.
- Duration of Response (DOR) by Investigator Review (All Cohorts) [ Time Frame: From first response to first disease progression or death, assessed up to 58 months ]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.
- Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) [ Time Frame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months ]Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
- Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts) [ Time Frame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months ]Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.
- Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) [ 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 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.
- Progression-Free Survival (PFS) by Investigator Review (All Cohorts) [ 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 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.
- Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: From first dose through 28 days after the last dose, assessed up to 75 months. ]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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Provide written informed consent
- Histologically confirmed cancers for which no curative therapy exists
- Documented HER2 or EGFR exon 18 mutation
- Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol
- At least one measurable lesion, defined by RECIST v1.1
Exclusion Criteria:
- Participants harboring ineligible somatic HER2 mutations
- Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible
- Participants who are receiving any other anticancer agents
- Symptomatic or unstable brain metastases
- Women who are pregnant or breast-feeding
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953926
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| Study Director: | Chief Scientific Officer | Puma Biotechnology, Inc. |
Documents provided by Puma Biotechnology, Inc.:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Puma Biotechnology, Inc. |
| ClinicalTrials.gov Identifier: | NCT01953926 |
| Other Study ID Numbers: |
PUMA-NER-5201 2013-002872-42 ( EudraCT Number ) |
| First Posted: | October 1, 2013 Key Record Dates |
| Results First Posted: | March 12, 2024 |
| Last Update Posted: | March 12, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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 Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| 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. |
| URL: | https://pumabiotechnology.com/data_sharing_policy.html |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Neratinib Nerlynx Breast Solid Tumors Cancer HER2 mutations EGFR mutations Fulvestrant Trastuzumab |
Cervical Salivary ERBB2 Exon 18 Metastatic HR Positive Lung Non-Small Cell Lung Cancer (NSCLC) |
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Neoplasms Paclitaxel Trastuzumab Fulvestrant Neratinib Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |
Antineoplastic Agents, Immunological Antineoplastic Agents, Hormonal Estrogen Receptor Antagonists Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |