Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations Clinical Trial
— SUMMITOfficial title:
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
| Verified date | February 2024 |
| Source | Puma Biotechnology, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 582 |
| Est. completion date | January 2, 2023 |
| Est. primary completion date | January 2, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Peter MacCallum Cancer Centre | East Melbourne | Victoria |
| Belgium | UZ Leuven | Leuven | |
| Canada | British Columbia Cancer Center | Vancouver | British Columbia |
| Denmark | University Hospital, Rigshospitalet | Kopenhagen | |
| France | Institut Bergonié | Bordeaux | |
| France | Centre Leon Berard | Lyon | |
| France | Institut Curie - Hopital Rene Huguenin | Saint-Cloud | Ile De France |
| France | Institut Gustave Roussy | Villejuif | Paris |
| Ireland | St. Vincent's University Hospital | Dublin | Leinster |
| Israel | Hadassah Medical Center | Jerusalem | |
| Israel | Davidoff Cancer Center, Rabin Medical Center | Petah Tikva | |
| Israel | Sheba Medical Center | Ramat Gan | |
| Israel | Kaplan Medical Center | Rehovot | |
| Israel | Sourasky Medical Center | Tel Aviv | |
| Italy | Azienda Socio Sanitaria Territoriale di Cremona | Cremona | |
| Italy | Istituto Europeo di Oncologia (IEO) I.R.C.C.S. | Milano | |
| Italy | Fondazione Policlinico Universitario Gemelli I.R.C.C.S. | Roma | |
| Italy | AOU Citta della Salute e della Scienza di Torino | Torino | |
| Korea, Republic of | Yonsei University Health System, Serverance Hospital | Seodaemun-Gu | Seoul |
| Serbia | Institute for Oncology and Radiology of Serbia | Belgrade | |
| Spain | Hospital Universitari Clinic Barcelona | Barcelona | |
| Spain | Hospital Universitario Quiron Dexeus | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Hospital Clinico Universitario San Carlos | Madrid | |
| Spain | Hospital Universitario Fundacion Jimenez Diaz | Madrid | |
| Spain | Hospital Universitario Madrid Sanchinarro (START Madrid) | Madrid | |
| Spain | Hospital Universitario Quiron Madrid | Madrid | |
| Spain | Hospital Clinico Universitario de Valencia | Valencia | |
| Spain | Instituto Valenciano de Oncologia | Valencia | |
| United Kingdom | Royal Free Hospital | London | |
| United States | University of Michigan | Ann Arbor | Michigan |
| United States | Winship Cancer Institute, Emory University | Atlanta | Georgia |
| United States | University of Alabama at Birmingham | Birmingham | Alabama |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Roswell Park Comprehensive Cancer Center | Buffalo | New York |
| United States | Northwestern University | Chicago | Illinois |
| United States | UT Southwestern Medical Center | Dallas | Texas |
| United States | City of Hope | Duarte | California |
| United States | The West Clinic | Germantown | Tennessee |
| United States | Saint Francis Cancer Center-Bon Secours | Greenville | South Carolina |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | Mayo Clinic Florida | Jacksonville | Florida |
| United States | Gundersen Center for Cancer and Blood Disorders | La Crosse | Wisconsin |
| United States | University of California, San Diego | La Jolla | California |
| United States | University of California, Los Angeles | Los Angeles | California |
| United States | University of Southern California | Los Angeles | California |
| United States | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin |
| United States | University of Miami | Miami | Florida |
| United States | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee |
| United States | Ochsner Clinic Foundation | New Orleans | Louisiana |
| United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
| United States | Stanford Cancer Center | Palo Alto | California |
| United States | Mayo Clinic Arizona | Phoenix | Arizona |
| United States | UPMC Magee-Woman's Hospital, Women's Cancer Center | Pittsburgh | Pennsylvania |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | Washington University | Saint Louis | Missouri |
| United States | Metro Minnesota Community Oncology Research Consortium | Saint Louis Park | Minnesota |
| United States | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | Kaiser Permanente NoCal (STRATA) | Vallejo | California |
| Lead Sponsor | Collaborator |
|---|---|
| Puma Biotechnology, Inc. |
United States, Australia, Belgium, Canada, Denmark, France, Ireland, Israel, Italy, Korea, Republic of, Serbia, Spain, United Kingdom,
Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018 Feb 8;554(7691):189-194. doi: 10.1038/nature25475. Epub 2018 Jan 31. Erratum In: Nature. 2019 Feb;566(7745):E11-E12. — View Citation
Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sorensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzalez-Farre X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov. 2020 Feb;10(2):198-213. doi: 10.1158/2159-8290.CD-19-0966. Epub 2019 Dec 5. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 |
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months | |
| Primary | 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 |
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months | |
| Primary | 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 |
From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks | |
| Secondary | 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 |
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months | |
| Secondary | 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. |
From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months. | |
| Secondary | 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. | From first response to first disease progression or death, assessed up to 58 months | |
| Secondary | 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. | From first response to first disease progression or death, assessed up to 58 months | |
| Secondary | 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. | From enrollment date to first documented response or stable disease =16, or =24 weeks for breast cancer, assessed up to 58 months | |
| Secondary | 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. | From enrollment date to first documented response or stable disease =16, or =24 weeks for breast cancer, assessed up to 58 months | |
| Secondary | 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. | 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 | |
| Secondary | 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. | 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 | |
| Secondary | 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 | From first dose through 28 days after the last dose, assessed up to 75 months. |