Abstract
CRESTONE: Initial efficacy and safety of seribantumab in solid tumors harboring NRG1 fusions
Journal of clinical oncology, Vol.40(16_suppl), pp.3006-3006
06/01/2022
DOI: 10.1200/JCO.2022.40.16_suppl.3006
Abstract
3006
Background: NRG1 fusions are rare oncogenic drivers found in ̃0.2% of all solid tumors. These fusions elicit ERBB3/HER3 overactivation to drive tumor growth and cancer cell survival. Currently there are no approved targeted therapies for NRG1 fusion-positive tumors. Furthermore, patients (pts) with tumors harboring NRG1 fusions have poor outcomes with standard therapies. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody that suppressed tumor growth in NRG1 fusion-driven preclinical models. Here, we present initial clinical data from the CRESTONE study (NCT04383210). Methods: CRESTONE is a Phase 2, global, multicenter, open-label study of seribantumab in adult pts with locally advanced or metastatic solid tumors harboring NRG1 fusions. A dose ranging phase established the RP2D as a 3g once weekly (QW) intravenous dose administered until treatment discontinuation criteria are met. In the expansion phase, cohort 1 will enroll at least 55 pts who had received at least one prior therapy and are naïve to ERBB-targeted therapy. Exploratory cohorts 2 or 3 will enroll pts previously treated with ERBB-targeted therapies and/or tumors harboring additional molecular alterations. The primary endpoint is objective response rate (ORR) by independent central review per RECIST v1.1. Initial data from cohort 1 pts who received seribantumab 3g QW with investigator (INV)-assessed response per RECIST v1.1 are reported. Results: By JAN-13-2022, 12 pts have received seribantumab 3g QW in cohort 1. Median age was 65 years (range 44–76), 67% were female, and median number of prior therapies was 1 (range 1–5). 92% (11/12) of pts had non-small cell lung cancer (NSCLC); 5 different NRG1 fusion partners ( ATP1B1, CD74, ITG B1, SDC4, SLC3 A2) were reported by local next-generation sequencing tests. Among 10 pts evaluable for INV-assessed response, the confirmed ORR was 30%, and the disease control rate was 90% (1 complete response, 2 partial responses, 6 stable disease, 1 progressive disease). 58% (7/12) of pts remain on study treatment, including 2 pts with NSCLC who achieved objective responses with an ongoing duration of response of 6 and 8.5 months. Seribantumab 3g QW was well tolerated with no drug discontinuations or dose reductions. Across all cohorts (n = 29), the most frequently (≥20%) reported treatment-related adverse events (TRAEs) were diarrhea (38%), fatigue (34%), and rash (24%), all were grade 1 or 2. One grade 3 TRAE of vomiting occurred; there were no Grade 4 or 5 TRAEs. Efficacy analysis is ongoing and updated efficacy data from evaluable pts in cohort 1 will be presented. Conclusions: Initial data indicate seribantumab induced durable responses in advanced solid tumors harboring NRG1 fusions and has a favorable safety profile. These data support the continued evaluation of seribantumab in NRG1 fusion-positive solid tumors in the ongoing CRESTONE study. Clinical trial information: NCT04383210.
Details
- Title: Subtitle
- CRESTONE: Initial efficacy and safety of seribantumab in solid tumors harboring NRG1 fusions
- Creators
- Daniel R. Carrizosa - Levine Cancer InstituteMark E. Burkard - University of Wisconsin Carbone Cancer CenterYasir Y Elamin - The University of Texas MD Anderson Cancer CenterJayesh Desai - Peter MacCallum Cancer CentreShirish M. Gadgeel - Henry Ford Health SystemJessica Jiyeong Lin - Massachusetts General HospitalSaiama Naheed Waqar - Washington University in St. LouisDavid R. Spigel - Sarah CannonYoung Kwang Chae - Northwestern UniversityParneet K. Cheema - William Osler Health SystemEric B. Haura - Moffitt Cancer CenterStephen V. Liu - Georgetown UniversityDanny Nguyen - City Of Hope National Medical CenterKaren L. Reckamp - Cedars-Sinai Medical CenterFrank Yung-Chin Tsai - HonorHealthValerie Malyvanh Jansen - New York Oncology HematologyAlexander E. Drilon - Memorial Sloan Kettering Cancer CenterSai-Hong Ignatius Ou - University of California, IrvineD. Ross Camidge - University of Colorado DenverTejas Patil - University of Colorado Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.40(16_suppl), pp.3006-3006
- DOI
- 10.1200/JCO.2022.40.16_suppl.3006
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Number of pages
- 1
- Language
- English
- Date published
- 06/01/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984700647202771
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