Phase I study of ABM-1310 as monotherapy and in combination with cobimetinib for BRAF-mutated advanced solid tumors: safety, efficacy, and dose expansion

The aim of this report is to provide accurate nationwide epidemiologic data on primary central nervous system (CNS) tumors in Korea. Despite its importance, there are no accurate statistics on primary CNS tumors in Korea. We analyzed primary CNS tumors diagnosed in 2005 from the nationwide registry. Data on primary CNS tumors diagnosed in 2005 were collected from the Korean Central Cancer Registry and the Korean Brain Tumor Society. Crude and age-standardized rates were calculated in terms of gender, age, and histological type. Tumors of uncertain histology were investigated individually at the corresponding hospitals and had their diagnoses confirmed. A total of 5,692 patients diagnosed with primary CNS tumors in 2005 were included in this study. CNS tumors occurred in females more often than in males (female to male, 1.43 : 1). The most common tumor was meningioma (31.2%). Glioblastoma accounted for 30.7% of all gliomas, and 19.3% of all malignant primary CNS tumors. In children under 19 years of age, both germ cell tumor and embryonal/primitive/medulloblastoma were the most common tumors. This article is the first nationwide primary CNS tumor epidemiology report in Korea. Data from this study should provide valuable information regarding the understanding of primary CNS tumors epidemiology in Korea.

BackgroundLarotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.MethodsPatients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR).ResultsAs of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. The 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3–4 in 3 patients. No new safety signals were identified.ConclusionsIn patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.

Primary central nervous system (CNS) tumours are heterogeneous, with different treatment pathways and prognoses depending on their histological and molecular classification. Due to their anatomical location, all CNS tumours, regardless of malignancy, can be debilitating. We used vital statistics linked to Canadian Cancer Registry data to estimate the age-standardized incidence rates (ASIR), Kaplan-Meier survival rates (SR), and limited-duration prevalence proportions (PP) of 25 histology-specific CNS tumour groups that were classified based on site and histology. During 2010-2017, 45,115 patients were diagnosed with 47,085 primary CNS tumours, of which 19.0% were unclassified. The average annual ASIR was 21.48/100,000 person-years and did not vary by sex. The ASIR increased with age, particularly for meningioma, unclassified tumours, and glioblastoma. The eight-year PP was 102.1/100,000 persons (index date 1 January 2018). The most common histology was meningioma (ASIR: 5.19; PP: 31.6). The overall five-year SR among 51,310 patients diagnosed during 2008-2017 was 57.2% (95% CI: 56.8-57.7%). SRs varied by tumour behaviour, histology, and patient age, with the lowest SR among glioblastoma patients (5-year SRs ranged from 1.3-25.7%). For non-malignant tumours, the 5-year SRs ranged from 37.4-100%. We provide the most up-to-date histology-specific surveillance estimates for primary CNS tumours in Canada.

Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.

Background. Central Nervous System (CNS) tumor is neoplasm that located in central nervous system, which include brain and medulla spinalis. Despite its significant raise of incidence and morbidities, limited epidemiological data was available. Therefore, this study aimed to describe the epidemiological characteristic of CNS tumor over a 3-year period in a single tertiary hospital in Bali, Indonesia. Methods. This study was a descriptive study with cross sectional design. This study included all patients aged 18 year or over who were histopathologically diagnosed with central nervous tumor at “Prof. Dr. I.G.N.G. Ngoerah General Hospital”, Denpasar, between January 2020 and December 2022. Data about age, gender, tumor location, histopathological type, tumor grading, and source of metastases in secondary CNS tumor were obtained from medical record. Result. A total of 221 cases were recorded during this study period. The prevalence of primary CNS tumor was 81.9% while secondary CNS tumor was 18.1%. The majority of case, both in primary and secondary CNS tumor were female in age group of 50-59. Supratentorial constituted the most common lesion site in primary and secondary CNS tumor. The most frequent histopathological type of primary CNS tumor was meningioma, making up 48.1% of cases, followed by diffuse astrocytic and oligodendroglial tumors (26.5%), and tumor of the cranial and paraspinal nerve (9.9%). Carcinoma is the most common histological type in secondary CNS tumor with lung and breast tumor being the majority source of secondary CNS tumor, found in 40% and 27.5%, respectively. Conclusion. Adult female with age of 50-59 is the most affected group in CNS tumor. Primary CNS tumor were commonly found in supratentorial with meningioma and WHO grade I being the most frequent histopathological type and grade. Secondary CNS tumor were mostly found in supratentorial and originated from primary lung tumor.

Metastases represent the most common type of intracranial neoplasm. In women, 30% of such tumors derive from breast carcinoma. In neurosurgical cases with ambiguous cellular morphology and/or limited biopsy material, immunohistochemistry (IHC) is often performed to distinguish metastases from primary central nervous system (CNS) neoplasms. IHC for mammaglobin-A (MGA), a protein expressed in a majority of breast carcinomas, is commonly applied in this setting, but its utility for distinguishing primary CNS neoplasms from metastatic breast carcinoma is unknown; the reactivity of MGA in primary and metastatic CNS neoplasms has never been described. Here, we describe the frequency and patterns of IHC reactivity for MGA in metastatic and primary CNS neoplasms from patients with well-documented histories of breast carcinoma. Following a published protocol previously applied to non-CNS neoplasms, MGA staining of moderate to strong intensity within 5% or more of a neoplasm was considered positive. On the basis of these criteria, 3 of 12 (25.0%) glioblastomas, 1 of 10 (10.0%) meningiomas, and 47 of 95 (49.5%) metastases were positive. Importantly, the cytoarchitectural staining characteristics among all 4 MGA-positive primary CNS neoplasms (cytoplasmic and nuclear) differed from those of the metastases (cytoplasmic and membranous). These findings suggest that MGA IHC staining intensity and distribution can distinguish metastases from primary CNS neoplasms (P=0.0086) in women with a history of breast carcinoma but also indicate that cytologic staining patterns must be interpreted for more accurate tumor classification.

Positive cerebrospinal fluid (CSF) cytology typically indicates leptomeningeal dissemination of metastatic, secondary, or rarely, primary central nervous system (CNS) tumors. To the authors' knowledge, large-scale studies on clinicocytologic features of various primary CNS tumors in CSF are lacking. The authors performed a retrospective cytomorphologic study on 127 positive CSF specimens from 87 patients with a history of primary nonhematologic CNS tumors. Pertinent clinical, radiological, and histologic findings were reviewed. Pediatric tumors accounted for the majority (82.6%) of the primary CNS tumors with positive CSF cytology. The most common radiological finding of neuraxial dissemination was diffuse leptomeningeal enhancement. Greater than 95% of the cases with positive CSF cytology were high-grade or malignant tumors. The most common tumor type was central primitive neuroectodermal tumors (47.2%). Overall, the frequency of initial metastasis was found to be lowest in central primitive neuroectodermal tumors and retinoblastomas (approximately one-third). They also had the longest latency (1.5-2 years) in cases without initial metastasis. The majority of metastatic tumors in CSF demonstrated distinct cytomorphology reminiscent of the histologic features of the primary tumor, such as prominent nucleoli, cell wrapping, and apoptosis in large cell/anaplastic medulloblastomas; rhabdoid morphology and cytoplasmic inclusions in atypical teratoid/rhabdoid tumors; large clusters of cells with scant cytoplasm and nuclear molding in retinoblastomas; nuclear pleomorphism and hyperchromasia in high-grade infiltrating astrocytomas; and small clusters/rosettes of epithelioid cells in ependymomas. The results of the current study provide useful clinicoradiological information and cytomorphologic findings for both common and rare primary CNS tumors that cytopathologists might encounter on CSF examination.

Thyroid transcription factor-1 (TTF-1) is a nuclear protein primarily recognized for its role in the development and differentiation of thyroid, lung, and certain diencephalic tissues. Although well-established as an immunohistochemical marker in thyroid and lung cancers, recent studies have explored its expression and diagnostic value in primary central nervous system (CNS) tumors. This systematic review aims to consolidate current knowledge on TTF-1 immunohistochemistry in primary CNS tumors, assessing its prevalence, diagnostic utility, and clinical implications. The review encompasses various CNS tumor types, including subependymal giant cell astrocytoma, chordoid glioma, pituicytoma, ependymomas, astrocytomas, glioblastomas, medulloblastomas, and choroid plexus tumors, highlighting the potential role of TTF-1 in differentiating these neoplasms from other CNS and metastatic tumors. By synthesizing findings from multiple studies, this review underscores the diagnostic value of TTF-1 in the neuropathological evaluation of CNS tumors and suggests directions for future research to refine its clinical application.

Liquid Biopsy for Evaluating Mutations and Chromosomal Aberrations in Cerebrospinal Fluid from Patients with Primary or Metastatic Central Tumors

e24146 Background: Primary central nervous system (CNS) tumors are a diverse group of neoplasms that can vary greatly in terms of their cellular origin, histological features, clinical behavior, and prognosis. Many diagnoses leave patients with a poor prognosis and an impaired quality of life. Palliative care (PC) has long been used as a means to improve quality of life and symptoms associated with debilitating malignancies; however, its use in CNS tumors is not well characterized. Yet, the plethora of life-altering symptoms such as gait impairment, cognitive decline, motor deficits, and seizures provide a need for further multidisciplinary approaches to integrating PC with primary CNS tumor diagnoses. We aim to assess factors that influence the receipt of PC in the current data on central nervous system tumor patients and assess differences in overall survival. Methods: This study retrospectively evaluated the use of PC in patients with single primary malignant central nervous system tumors (gliomas, neuroepitheliomatous neoplasms, and meningiomas) diagnosed and recorded in the National Cancer Database (NCDB) between 2004 and 2020. Patients were identified by ICD-O-3 coding and patients with other malignancies were excluded. Multivariable logistic regression was performed to evaluate associations between patient characteristics and the use of PC, and Kaplan-Meier curves with log-rank analysis were used to determine survival for each group. Results: After excluding patients without information on utilization of PC, a total of 9295 patients with primary CNS tumors were considered in the final analysis. Overall, 1.31% received palliative care. From patients receiving palliative care, 81.1-93.4% received non-curative treatment with surgery, radiation, chemotherapy, or a combination of one or more of these modalities with additional pain management. Odds of receiving palliative care were decreased in black patients, patients who received non-palliative surgical treatment, patients with a primary tumor site at the optic chiasm, patients with unilateral tumors, and patients with private, medicaid, other government, or unknown insurance status. Odds of receiving palliative care were increased with increased Charlson-Deyo Score, in patients receiving non-palliative systemic or radiation treatment, and patients with a primary site at the spinal dura. Utilization of PC was associated with a decreased 1-year and 5-year overall survival. Conclusions: PC use in CNS tumors was influenced by tumor location, treatment type, insurance status, patient race, and comorbidity index. This study demonstrates the areas in which use of PC utilization is still lacking across a diverse set of CNS tumors and patients. Further exploration is needed into the integration of palliative care broadly across these malignancies as it still remains low despite the abundance of quality-of-life altering symptoms.

Purpose: In recent decades, the survival outcomes among adolescent and young adults (AYAs, 15-39 years) have not improved substantially, especially among AYAs with primary central nervous system (CNS) tumors. While this is likely multifactorial, low participation in clinical trials among AYAs is thought to be a critical contributing factor. In this study, we describe the pattern of clinical trial enrollment among AYAs with primary CNS tumors at our institution. Methods: We performed a retrospective, IRB-approved chart review of AYAs with CNS tumors treated at the Dana-Farber Cancer Institute (DFCI) between January 2009 and December 2018. We used logistic regression analyses and descriptive statistics to analyze this sample and determine the clinical trial enrollment at the pediatric affiliate (Dana-Farber/Boston Children's Cancer and Blood Disorders Center) and adult affiliate (Dana-Farber/Brigham and Women's Cancer Center). Results: Ninety-three AYA patients with primary CNS tumors were treated at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, while 507 patients with primary CNS gliomas were treated at the Dana-Farber/Brigham and Women's Cancer Center. At the pediatric affiliate, 35.4% (33/93) of AYAs were enrolled in a therapeutic clinical trial, while at the adult affiliate, 15.8% (80/507) of AYAs were enrolled in a clinical trial. High-grade gliomas were associated with significantly higher rates of enrollment in the adult affiliate. Conclusions: Clinical trial enrollment remains poor among AYAs with CNS tumors, and clinical trial enrollment participation is modestly higher in the pediatric setting. Our study demonstrates the continued need to evaluate and address factors associated with clinical trial enrollment among AYAs with CNS tumors.

PurposeThe purpose of this study was to determine the epidemiologic characteristics and survival of patients with primary brain and other central nervous system (CNS) tumors in Korea and to compare our findings with those from the United States.Materials and MethodsWe collected data on primary brain and CNS tumors diagnosed between 2007 and 2016 from the Korea Central Cancer Registry. The age-standardized incidence rates (ASRs) and 5-year relative survival rates (RSRs) were evaluated. We applied the classification and definitions of the Central Brain Tumor Registry of the United States to our analysis for direct comparison with United States data.ResultsA total of 115,050 primary brain and CNS tumors were identified, and the ASR of all tumors was 22.01 per 100,000 individuals, which was lower than the 23.41 in the United States. However, the ASR of malignant tumors was significantly lower herein (4.27) than in the United States (7.08). Meningeal tumors were the most common histologic group among all tumors (ASR, 8.32). The 5-year RSR of all primary brain and other CNS tumors was 86.4%, and that of all malignant tumors was 44.1%, which was higher than the 35.8% observed in the United States. Among malignant tumors, glioblastomas had the lowest 5-year RSR (12.1%).ConclusionIn Korea, malignant brain and other CNS tumors have a lower incidence and better survival outcome.

Central nervous system (CNS) tumours occur when abnormal cells form in the tissues of the brain and/or spinal cord. Conventional testing for CNS tumour classification involves histopathological evaluation and molecular markers. More recently, DNA methylation-based classifier tests are being used as an adjunct tool in addition to conventional tests to help with CNS tumour classification. We conducted a health technology assessment of DNA methylation-based classifier tests for CNS tumours, which included an evaluation of effectiveness, cost-effectiveness, and budget impact of publicly funding DNA methylation-based classifier tests for CNS tumours. After considering the likely effects of testing on the patient experience, we determined not to perform an analysis of patient preferences and values. We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria.We performed a systematic economic literature search and developed a decision-analytic model to evaluate the cost-effectiveness of using DNA methylation-based classifier tests. We also analyzed the budget impact of publicly funding DNA methylation-based classifier tests. All costs were expressed in 2024 CAD. We included 38 studies in the clinical evidence review. Compared with conventional testing alone, DNA methylation-based classifier tests are an adjunct tool that may improve CNS tumour classification (GRADE: Moderate). The tests may improve downstream patient outcomes, although the evidence is very uncertain (GRADE: Very low). Unclassifiable test results may increase time to treatment, but the evidence is very uncertain (GRADE: Very low).We did not identify any studies that met the inclusion criteria for our economic literature review. We estimated that there were about 716 patients with challenging diagnostic primary CNS tumours in Ontario each year. The cost of clinical-based DNA methylation profiling for CNS tumours was $1,500 per patient. The annual incremental costs of second-tier DNA methylation classifier tests (after the use of conventional test) would be $1,074,738 for all challenging diagnostic cases, and DNA methylation-based classifier tests improved the diagnosis for 195 patients. The incremental cost-effectiveness ratio (ICER; i.e., the incremental cost per case with an improvement in primary CNS tumour classification) was $5,521. Scenario analyses showed that for children aged 0 to 14 years, the ICER was reduced to $2,683. Publicly funding second-tier DNA methylation-based classifier testing for challenging diagnostic cases of primary CNS tumours would result in a budget increase of about $1 million per year, with total additional costs of about $5.4 million over 5 years to test 3,600 patients. The budget increase for funding subgroup populations (e.g., children, patients with malignant tumours) would be smaller. If DNA methylation-based classifiers are used as first-tier tests for all patients with newly diagnosed primary CNS tumours, the additional funding costs would be about $4 million per year, with total additional funding costs of about $21 million over the initial 5-year period. DNA methylation-based classifier tests are an adjunct tool that may improve CNS tumour classification compared with conventional testing alone. Given that there are no empirical willingness-to-pay thresholds for an improvement in primary CNS tumour classification, the cost-effectiveness of DNA methylation-based classifier cannot be determined. Publicly funding second-tier DNA methylation-based classifier tests for challenging diagnostic primary CNS tumours would result in a total budget increase of about $5.4 million over 5 years. Public funding DNA methylation-based classifiers as first-tier tests for all patients with newly diagnosed primary CNS tumours would result in total budget increase of around $21 million over the next 5 years.

2002 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions are oncogenic drivers in various tumor types, including central nervous system (CNS) tumors. Larotrectinib is a first-in-class, highly selective TRK inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer, with an objective response rate (ORR) of 78% across 175 adult and pediatric patients with various non-CNS cancers (McDermott et al, ESMO 2020). We report data on patients with TRK fusion-positive primary CNS tumors. Methods: Patients with primary CNS tumors harboring an NTRK gene fusion enrolled in two clinical trials (NCT02637687, NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Response was investigator assessed. Results: As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified: 19 high-grade gliomas (HGG), 8 low-grade gliomas (LGG), 2 glioneuronal tumors, 2 neuroepithelial tumors, 1 CNS neuroblastoma, and 1 small round blue cell tumor. The patients had gene fusions involving NTRK2 (n = 24; 73%), NTRK1 (n = 5; 15%), and NTRK3 (n = 4; 12%). Median age was 8.9 years (range 1.3–79.0); 26 patients were pediatric ( < 18 years). Patients were heavily pre-treated with 45% having 2 or more prior lines of systemic therapy. The ORR in all patients was 30% (95% CI 16–49): 3 complete responses (all in pediatric patients), 7 partial responses (2 pending confirmation), 20 stable disease (including 15 pts > 6 months), and 3 progressive disease. The ORR in patients with HGG and LGG were 26% (95% CI 9–51) and 38% (95% CI 9–76), respectively. In all patients, the 24-week disease control rate was 73% (95% CI 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The median time to response was 1.9 months. Median duration of response (DoR) was not reached (95% CI 3.8–not estimable [NE]) at a median follow-up of 12.0 months. The 12-month DoR rate was 75% (95% CI 45–100). Median PFS was 18.3 months (95% CI 6.7–NE) at a median follow-up of 16.5 months. Median overall survival (OS) was not reached (95% CI 16.9–NE) at a median follow-up of 16.5 months, with a 12-month OS rate of 85% (95% CI 71–99). Duration of treatment ranged from 1.2 to 31.3+ months. Treatment-related adverse events (TRAE) were reported by 20 patients and were Grade 3–4 in 3 patients (9%). There were no treatment discontinuations due to TRAEs. Conclusions: In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile. These results support testing for NTRK gene fusions in patients of all ages with CNS tumors. Clinical trial information: NCT02637687, NCT02576431.

10050 Background: Entrectinib is a TRK and ROS1 inhibitor that has shown rapid and durable responses in children with NTRK1/2/3 or ROS1 fusion-positive (fp) extracranial solid or primary CNS tumors in an integrated analysis of the STARTRK-NG (NCT02650401), TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267) trials. These data led to FDA and EMA approval of entrectinib in pediatric patients > 1 month with NTRK fp tumors. Here we present updated data on pediatric patients with ROS1 fp tumors based on the trials listed above to further describe the efficacy and safety of entrectinib in this population. Methods: Eligible pts were TRK/ROS1 inhibitor-naïve, < 18 years old, with locally advanced/metastatic extracranial solid or primary CNS tumors, with measurable or evaluable-only disease. All pts who received ≥1 daily dose of oral entrectinib are included in the safety-evaluable population. Pts who had a ROS1 fusion and were followed for ≥6 months are included in the ROS1 efficacy-evaluable population. Pts received entrectinib until disease progression, unacceptable toxicity, or consent withdrawal. Tumor responses were confirmed by blinded independent central review (BICR) per RECIST v1.1 or RANO criteria. Primary endpoint: confirmed objective response rate (ORR) per BICR. Key secondary endpoints: ORR in pts with baseline measurable disease per BICR; duration of confirmed response (DoR); time to confirmed response (TTR); clinical benefit rate (CBR); progression-free survival (PFS); overall survival (OS); safety. Results: At clinical cut-off (16 July 2024), of the 113 safety-evaluable pts, there were 26 pts in the ROS1 efficacy-evaluable cohort. ORR was 69.2% (95% CI 48.2, 85.7). Median TTR was 1.84 months. Median OS was not evaluable. Median duration of survival follow-up was 29.4 months (range 1–80). Efficacy outcomes are shown in the table. The most common related adverse events were weight gain (37.2%), anemia (36.3%), and AST increase (26.5%). Related fracture events occurred in 23% of pts. Conclusions: Entrectinib yielded rapid and durable responses in pediatric pts with ROS1 fp extracranial solid or primary CNS tumors. The safety profile of entrectinib was consistent with previous reports. Clinical trial information: NCT02650401 ; NCT04589845 ; NCT02568267 . Efficacy ROS1 (N=26) Confirmed ORR*, N, % [95% CI] 18, 69.2 [48.2- 85.7] Complete response 4, 15.4 [4.4- 34.9] Partial response 14, 53.8 [33.4- 73.4] Median confirmed DoR*, months (95% CI) NE (16.2- NE) Median TTR*, months (range) 1.84 (1.6- 4.0) CBR*, % (95% CI) 84.6 (65.1- 95.6) Median PFS*, months (95% CI) NE (21.8- NE) Median OS, months (95% CI) NE (NE- NE) *Per BICR; CI, confidence interval; NE, not evaluable.