Treatment-related Adverse Events Research Articles

JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam.

Risdiplam is a once-daily oral, survival of motor neuron 2 (SMN2) splicing modifier approved for the treatment of spinal muscular atrophy (SMA). JEWELFISH (NCT03032172) investigated the safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamic (PD) relationship of risdiplam in non-treatment-naïve patients with SMA. JEWELFISH enrolled adult and pediatric patients (N = 174) with confirmed diagnosis of 5q-autosomal recessive SMA who had previously received treatment with nusinersen (n = 76), onasemnogene abeparvovec (n = 14), olesoxime (n = 71), or were enrolled in the MOONFISH study (NCT02240355) of the splicing modifier RG7800 (n = 13). JEWELFISH was an open-label study with all participants scheduled to receive risdiplam. The most common adverse event (AE) was pyrexia (42 patients, 24%) and the most common serious AE (SAE) was pneumonia (5 patients, 3%). The rate of AEs and SAEs decreased by > 50% from the first to the second year of treatment, and there were no treatment-related AEs that led to withdrawal from treatment. An increase in SMN protein in blood was observed following risdiplam treatment and sustained over 24months of treatment irrespective of previous treatment. Exploratory efficacy assessments of motor function showed an overall stabilization in mean total scores as assessed by the 32-item Motor Function Measure, Hammersmith Functional Motor Scale-Expanded, and Revised Upper Limb Module. The safety profile of risdiplam in JEWELFISH was consistent with previous clinical trials of risdiplam in treatment-naïve patients. Exploratory efficacy outcomes are reported but it should be noted that the main aim of JEWELFISH was to assess safety and PK/PD, and the study was not designed for efficacy analysis. TRIAL REGISTRATION: The study was registered (NCT03032172) on ClinicalTrials.gov on January 24, 2017; First patient enrolled: March 3, 2017.

Camrelizumab plus famitinib in previously chemo-immunotherapy treated patients with advanced NSCLC: results from an open-label multicenter phase 2 basket study

BackgroundThe combination of immune checkpoint inhibitors and antiangiogenic agents has been effective in treating multiple cancers. This was further explored in an open-label, multicenter phase 2 basket study (NCT04346381), which evaluated the antitumor activity and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (a receptor tyrosine kinase inhibitor) in patients with advanced solid tumors. We herein report the findings from the cohort of advanced NSCLC patients who progressed after treatment with platinum-doublet chemotherapy and immunotherapy.MethodsEligible patients were enrolled and treated with camrelizumab (200 mg once every 3 weeks via intravenous infusion) and oral famitinib (20 mg once daily). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.ResultsForty patients were enrolled in this cohort, with a median follow-up duration of 11.5 months. Three patients (7.5%) achieved a partial response, and 29 patients (72.5%) achieved stable disease. The ORR and DCR with this combination regimen were 7.5% (95% CI, 1.6–20.4) and 80.0% (95% CI, 64.4–90.9), respectively. The median DoR was 12.1 months (95% CI, 10.3-not reached). The median PFS was 5.4 months (95% CI, 4.1–7.5), and the median OS was 12.1 months (95% CI, 9.1–16.7). The estimated 12-month OS rate was 51.5% (95% CI, 34.9–65.9). The most frequent grade 3 or higher treatment-related adverse events occurring in more than 5% of patients included hypertension (27.5%), palmar-plantar erythrodysesthesia syndrome (10%), decreased neutrophil count (10%), and proteinuria (7.5%).ConclusionCamrelizumab plus famitinib demonstrated favorable benefits in PFS and OS, along with manageable safety profiles, in patients with advanced NSCLC who progressed after platinum-doublet chemotherapy and immunotherapy. This finding warrants further exploration.

Futibatinib: A Review in Locally Advanced and Metastatic Cholangiocarcinoma.

Futibatinib (LYTGOBI®) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR)1-4. It is approved in the EU, Japan and the USA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma (CCA) harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy. In the phase II part (FOENIX-CCA2) of a multinational phase I/II study in this patient population, monotherapy with futibatinib 20mg once daily was associated with clinically meaningful and durable responses, sustained health-related quality of life (HR-QOL), and a manageable safety profile with supportive care and as-needed dose modifications. Indeed, hyperphosphataemia (the most common all grade and grade 3 treatment-related adverse event) was manageable with phosphate-lowering therapy and dose reductions or interruptions. Although further efficacy and tolerability data are expected, current evidence indicates that futibatinib is a valuable targeted therapy option for adults with locally advanced or metastatic CCA harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy, a patient population with limited treatment options and poor life expectancy.

First-Line Nivolumab and Relatlimab Plus Chemotherapy for Gastric or Gastroesophageal Junction Adenocarcinoma: The Phase II RELATIVITY-060 Study

PURPOSE Open-label phase II study (RELATIVITY-060) to investigate the efficacy and safety of first-line nivolumab, a PD-1–blocking antibody, plus relatlimab, a lymphocyte-activation gene 3 (LAG-3)–blocking antibody, plus chemotherapy in patients with previously untreated advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC). METHODS Patients with unresectable, locally advanced or metastatic GC/GEJC were randomly assigned 1:1 to nivolumab + relatlimab (fixed-dose combination) + chemotherapy or nivolumab + chemotherapy. The primary end point was objective response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) in patients whose tumors had LAG-3 expression ≥1%. RESULTS Of 274 patients, 138 were randomly assigned to nivolumab + relatlimab + chemotherapy and 136 to nivolumab + chemotherapy. Median follow-up was 11.9 months. In patients with LAG-3 expression ≥1%, BICR-assessed ORR (95% CI) was 48% (38 to 59) in the nivolumab + relatlimab + chemotherapy arm and 61% (51 to 71) in the nivolumab + chemotherapy arm; median progression-free survival (95% CI) by BICR was 7.0 months (5.8 to 8.4) versus 8.3 months (6.9 to 12.1; hazard ratio [HR], 1.41 [95% CI, 0.97 to 2.05]), and median overall survival (95% CI) was 13.5 months (11.9 to 19.1) versus 16.0 months (10.9 to not estimable; HR, 1.04 [95% CI, 0.70 to 1.54]), respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 69% and 61% of all treated patients, and 42% and 36% of patients discontinued because of any-grade TRAEs in the nivolumab + relatlimab + chemotherapy and nivolumab + chemotherapy arms, respectively. CONCLUSION RELATIVITY-060 did not meet its primary end point of improved ORR in patients with LAG-3 expression ≥1% when relatlimab was added to nivolumab + chemotherapy compared with nivolumab + chemotherapy. Further studies are needed to address whether adding anti–LAG-3 to anti–PD-1 plus chemotherapy can benefit specific GC/GEJC patient subgroups.

Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Patient-reported outcomes of topical finasteride/minoxidil treatment for male androgenetic alopecia: A retrospective study using telemedical data.

Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.

Efficacy and safety of onasemnogene abeparvovec for the treatment of patients with spinal muscular atrophy type 1: A systematic review with meta-analysis.

Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety. Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence. This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable. Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated. The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study

PurposeThe optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC.Materials and methodsWe conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025).ConclusionFollowing neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer.

The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250mg orally, once daily) plus toripalimab (240mg intravenously, once every threeweeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥  3 treatment-related adverse events occurred in 28 (46.7%) patients. Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. gov NCT04169672.

ATR inhibitor, camonsertib, dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study).

Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects. Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating-tumor-DNA (ctDNA)-based molecular response rate. The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (HR = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity. The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering significantly reduced anemia incidence without any compromise to efficacy.

Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study

AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell–mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day–1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.

Efficacy and safety of transarterial chemoembolization combined with targeted therapy and immunotherapy versus with targeted monotherapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma (HCC) has gained increasing attention. However, there are variations in the efficacy and safety outcomes between TACE-T-I versus TACE combined with targeted drugs (TACE-T). This study aims to systematically evaluate the efficacy and safety of TACE-T-I versus TACE-T in unresectable HCC. PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 21, 2023, for comparative studies on TACE-T-I versus TACE-T for unresectable HCC. Outcome measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (TRAEs). OS was the primary outcome of this study. Weighted mean difference (WMD) or hazard ratio (HR) was used as the pooled statistic for OS and PFS. Relative risk (RR) was employed as the pooled statistic for ORR, DCR and the incidence of TRAEs. And 95% confidence intervals (CIs) were calculated for all effect measures. Data analysis was conducted using Stata 14.0 software. The meta-analysis included 14 studies with 2144 patients. The pooled results showed that compared with patients in the TACE-T group, patients in the TACE-T-I group had higher ORR (RR = 1.61; 95%CI: 1.38-1.89) and DCR (RR = 1.17; 95%CI: 1.09-1.26). Patients in the TACE-T-I group experienced prolonged PFS (WMD = 3.08; 95%CI: 2.63-3.53) and OS (WMD = 5.76; 95%CI: 4.68-6.84). And the risk of disease progression (HR = 0.45; 95%CI: 0.37-0.55) and death (HR = 0.43; 95%CI: 0.38-0.49) was lower in the TACE-T-I group. Common TRAEs included fever, pain, abdominal pain, nausea, vomiting, elevated ALT, elevated AST, hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence and severity of TRAEs in the TACE-T-I group were similar to those in the TACE-T group, with no significant differences (P > .05). Current evidence suggests that, on the basis of TACE combined with targeted therapy, the addition of immunotherapy provides better clinical efficacy and survival benefits for unresectable HCC patients, with good tolerability.

Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind phase I study in healthy subjects

ABSTRACT Background SHEN26, an oral broad-spectrum antiviral drug, possesses potent preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a favorable safety profile. Methods We report safety, tolerability, and pharmacokinetic data from a randomized, double-blind, placebo-controlled phase I study of SHEN26. Eighty-six healthy subjects were enrolled in the three studies: a single ascending-dose study (SAD), a multiple ascending-dose study (MAD), and a food-effect study (FE). Results In the SAD trial, the maximum observed plasma concentration (Cmax) and area under the curve (AUC) of the SHEN26 rapid metabolite SHEN26-69-0 increased approximately dose-proportionally in the 50–400 mg fasting dose range. In the 800 mg dose group, standard meals increased the Cmax and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of Cmax and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (Tmax) and increased the Cmax and AUC of SHEN26-69-0 compared with fasting administration. Most treatment-related adverse events were mild and resolved without treatment. Conclusion SHEN26 demonstrated satisfactory safety and tolerability in healthy subjects, which supports the continued study of SHEN26 against SARS-CoV-2. Trial Registration The trial is registered in ClinicalTrials.gov (CT. gov identifier: NCT05504746).

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma. This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2). The actual administered dose within DLs was dependent on weight. Safety was assessed in all DLs; PK analysis was conducted in DL2. Patients receiving once-weekly ONC201 (D1) served as a PK comparator. Twelve patients received D1D2 ONC201 (DL1, n = 3; DL1, n = 3; DL2, n = 6); no dose-limiting toxicities or grade ≥3 treatment-related adverse events occurred. PK analyses at DL2 (D1-250 mg, n = 3; D1-625 mg, n = 3; D1D2-250 mg, n = 2; D1D2-625 mg, n = 2) demonstrated variability in Cmax, AUC0-24, and AUC0-48, with comparable exposures across weight groups. No accumulation occurred with D1D2 dosing; the majority of ONC201 cleared before administration of the second dose. Cmax was variable between groups but did not appear to increase with D1D2 dosing. AUC0-48 was greater with D1D2 than once-weekly. ONC201 given D1D2 was well tolerated at all DLs and associated with greater AUC0-48.

Abstract RF02-05: Report on Cohort Expansion of Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of BB-1701 in Patients with Locally Advanced/Metastatic HER2 Low Breast Cancer

Abstract Background: BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized IgG1κ monoclonal anti-HER2 antibody with the same sequence as trastuzumab and eribulin linked together by a cathepsin-cleavable valine-citrulline linker. Eribulin is an inhibitor of microtubule approved for the treatment of metastatic breast cancer and advanced liposarcoma, following prior therapies. When BB-1701 targets HER2 expressing cancer cells and it is internalized, free eribulin is cleaved from the ADC by cathepsin b and causes cytotoxicity to cancer cells. The neighboring cells were affected with bystander effects, like cytotoxicity on tumor cells and non-cytotoxic effects on microenvironment, by free eribulin released from dying cancer cells. Here, we report preliminary results from the ongoing cohort expansion of a phase I study of BB-1701 in patients with HER2 low breast cancer (ClinicalTrials.gov Identifier: NCT 04257110). Methods: Patients ≥ 18 years of age with confirmed locally advanced/metastatic HER2 low breast cancer (IHC 2+ and FISH negative or IHC 1+), that had progressed on at least two lines of prior standard therapies, with ECOG PS ≤ 2 and measurable disease (RECIST 1.1) were enrolled. HER2 expressions was determined by IHC and FISH before enrollment. Total of four dose levels of BB-1701 (1.0 mg/kg Q3W, 1.2 mg/kg Q3W, 1.4 mg/kg Q3W and 1.6 mg/kg Q3W) were administered during the cohort expansion. The safety, tolerability and preliminary anti-tumor activity of BB-1701 were assessed during study. Radiographic assessment was conducted every 6 weeks. Results: As of 30 June 2023, 40 patients with HER2 low breast cancer were enrolled in the four dose levels, 5 patients at 1.0 mg/kg Q3W, 20 patients at 1.2 mg/kg Q3W, 5 patients at 1.4 mg/kg Q3W and 10 patients at 1.6 mg/kg Q3W. Median age was 55 years (range 30-74), 97.5% were female, and 30.0%/70.0% patients were ECOG PS 0/1. The median prior lines of systemic therapy were 3 (range 2 – 9). All subjects experienced at least one treatment emergent adverse events and treatment-related adverse events (TRAEs) occurred in 30 subjects. The most common all grade TRAEs (≥20%) were peripheral neuropathy, aspartate aminotransferase increased, alanine aminotransferase increased, anemia, white blood cell count decreased. Grade 3 TRAEs were peripheral neuropathy (3 subjects), peripheral sensory neuropathy (2 subjects), neutrophil count decreased (2 subjects), platelet count decreased (1 subject), white blood cell count decreased (1 subject). There were no grade 4 or grade 5 events. The treatment related serious adverse events (SAEs) were peripheral sensory neuropathy (1 subject) and infusion related reaction (1 subject). There was no interstitial lung disease reported. No patients discontinued the study treatment due to AE. Of the 40 patients enrolled, 38 patients were evaluable for antitumor activity. At 1.0 mg/kg dose level, of 5 patients treated, 2 achieved partial response (PR), 2 had stable disease (SD), best overall response rate (BOR) was 40.0% (2/5) and disease control rate (DCR) was 80.0% (4/5). At 1.2 mg/kg dose level, of 18 patients treated, 5 achieved PR, 11 had SD with BOR of 27.8% (5/18) and DCR of 88.9% (16/18). At 1.4 mg/kg dose level, of 5 patients treated, 2 achieved PR, 2 had SD with BOR of 40.0% (2/5), and DCR was 80.0% (4/5). One patient who achieved PR was previously progressed on sacituzumab govitecan. At 1.6 mg/kg dose level, of 10 patients treated, 1 achieved CR, 3 achieved PR, 2 had SD with BOR of 40.0% (4/10), and DCR of 60.0% (6/10). Among these patients, the patient who achieved CR was previously treated by disitamab vedotin, and one patient who achieved PR was previously treated by trastuzumab deruxtecan. Conclusions: BB-1701 has demonstrated promising preliminary antitumor activity in HER2 low breast cancer including patients who received prior anti-HER2 ADCs, and a manageable safety profile. Citation Format: Fei Ma, Pamela Munster, Xiaoxiang Guan, Jingfen Wang, Herui Yao, Erika Hamilton, Xian Wang, Yehui Shi, Xinjun Liang, Nong Xu, Huoling Tang, Yuhong Zhou, Ziping Wei. Report on Cohort Expansion of Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of BB-1701 in Patients with Locally Advanced/Metastatic HER2 Low Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF02-05.

Abstract RF01-04: Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification

Abstract Background: Fibroblast growth factor receptor 1 (FGFR1) gene amplification and overexpression is associated with an adverse prognosis in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) breast cancer and is observed in ~10% of all invasive breast cancers. The phase 2 FOENIX-MBC2 study (NCT04024436) was designed to evaluate the effect of futibatinib, a highly selective and potent irreversible covalent inhibitor of FGFR1–4 (FDA-approved for intrahepatic cholangiocarcinoma), used either alone or in combination with fulvestrant in patients with metastatic breast cancer. Here, we report final efficacy and safety data for the cohort of patients receiving futibatinib plus fulvestrant for HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification. Methods: Patients were eligible if they had disease progression after prior therapy for advanced/metastatic disease, had measurable disease per RECIST v1.1, had an ECOG performance status of 0 or 1, were fulvestrant-naïve, and had previously received 1–2 endocrine-containing therapies, ≤1 chemotherapy regimen, and a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for advanced cancer (unless ineligible). High-level FGFR1 gene amplification, determined in tumor tissue using next-generation sequencing, fluorescence in situ hybridization (FISH), or similar assays, was defined as FGFR1/centromere 8 ratio ≥5 or FGFR1 copy number ≥10 signals per cell. Local FGFR1 determination results were confirmed in tumor tissue by a central laboratory using FISH. Patients received oral futibatinib 20 mg once daily and standard fulvestrant dosing until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary endpoint was the 6-month progression-free survival (PFS) rate. Key secondary endpoints included objective response rate (ORR), PFS, and overall safety. Results: Overall, 22 female patients were enrolled in this cohort. Patients were a median age of 58 years, had received a median of 3 lines of any prior systemic anticancer therapy, and had all received CDK4/6 inhibitor pretreatment. PFS at 6 months was observed in 10 (45.5%) patients (95% CI: 24.4, 67.8) and the median PFS was 7.2 (95% confidence interval [CI]: 2.1, 7.6) months. Four patients had a confirmed partial response (ORR: 18.2%; 95% CI: 5.2, 40.3). The median duration of response was 6.3 (range: 3.3–12.8) months. All patients had ≥1 treatment-related adverse event (TRAE), the most common being hyperphosphatemia (95.5%), alopecia (54.5%), constipation (45.5%), and dry mouth (40.9%). There were 5 (22.7%) patients with a Grade 3 TRAE (no Grade 4 or 5). TRAEs leading to study treatment interruption or reduction were seen in 9 (40.9%) and 15 (68.2%) patients, respectively. There were 2 (9.1%) patients who had TRAEs leading to study treatment discontinuation. No treatment-related serious adverse events were reported. Conclusions: Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing. Citation Format: Senthil Damodaran, Fabrice André, Nisha Unni, Marta Ferreira, Karthik Giridhar, Brooke Daniel, Marco Colleoni, Luis Costa, Thomas Bachelot, Ciara O’Brien, Gail Wright, Masashi Shimura, Gareth Tomlinson, Maciej Gil, Nicholas Turner. Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF01-04.

Abstract RF01-07: The efficacy and safety of tinengotinib in patients with advanced or metastatic HR+/HER2- breast cancer or TNBC

Abstract Background: Tinengotinib is a novel multiple kinase inhibitor that strongly inhibits Aurora A/B, FGFR1/2/3, VEGFRs, JAK1/2, and CSF1R. Here we present the preliminary safety, pharmacokinetic and efficacy data of tinengotinib in patients (pts) with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) and triple-negative BC (TNBC) from Phase I TT420X2101 (NCT03654547) and Phase Ib/II TT420X1103 (NCT04742959) trials. Methods: Eligible pts with HR+/HER2- BC or TNBC who have no available standard therapeutic treatment options were enrolled to the TT420X2101 and TT420X1103 trials. Tinengotinib was given as monotherapy at different dose levels (5 mg QD, 10 mg QD and 12 mg QD); different dosing schedule (6 mg BID); and as combination (tinengotinib 8 mg QD and Abraxane 100 mg/m2). Recruitment spanned from January 2019 to March 2023. Results: As of June 2023, 36 pts with metastatic BC were treated: 30 with tinengotinib monotherapy at dose levels of 5 mg QD (n=1), 8 mg QD (n=4), 10 mg QD (n=5), 12 mg QD (n=18), 6 mg BID (n=2) and 6 with tinengotinib 8 mg QD in combination with nab-paclitaxel 100 mg/m2. Median age 51 years (range 24-75), ECOG PS 1 in 83.3% of pts, median lines of prior therapy were 5, and 77.8% of pts had prior taxanes. Of 30 pts receiving tinengotinib monotherapy, treatment related adverse events (TRAEs) were reported in 26 (86.7%) pts. 43.4% were Grade (G) 1-2, 43.3% were G3. No G4 or G5 TRAEs were reported. Common TRAEs (≥20%) of tinengotinib monotherapy were hypertension (60.0%), stomatitis (50.0%), palmar-plantar erythrodysesthesia syndrome (46.7%) and diarrhea (20.0%). All six (100%) pts receiving tinengotinib in combination with nab-paclitaxel experienced TRAEs, 16.7% were G1, 66.7% were G3, no G4 TRAEs, and one pt had G5 (pulmonary hemorrhage). Common TRAEs (≥20%) of tinengotinib in combination with nab-paclitaxel were neutrophil count decreased/neutropenia (50.0%), stomatitis (50.0%), hypertension (33.3%), hyponatremia (33.3%), hypokalemia (33.3%), and nausea (33.3%). Twenty-eight pts receiving tinengotinib monotherapy were efficacy evaluable. 11 pts with HR+/HER2- BC achieved objective response rate (ORR) of 45.5%, clinical benefit rate (CBR, CR+PR+SD ≥ 24 weeks) of 54.5% and median progression-free survival (mPFS) of 5.55 (95% CI 1.97-6.18) months. Partial responses were seen in 3 pts with HER2-zero (n=5) and 2 pts with HER2 low (1+/2+) pts (n=6), respectively. 17 pts with TNBC had ORR of 23.5%, CBR of 29.4% and mPFS of 2.73 (95% CI 1.68-6.41) months. In 6 pts treated with tinengotinib in combination with nab-paclitaxel, one out of 2 pts with HR+/HER2- BC achieved PR for 13 weeks as of data cutoff; two out of 4 pts with TNBC had SD. No significant difference in exposure was observed between tinengotinib monotherapy and tinengotinib in combination with nab-paclitaxel. Conclusions: Tinengotinib for the treatment of HR+HER2- BC or TNBC, whether as monotherapy or in combination with nab-paclitaxel, had manageable side effects. Tinengotinib has shown promising clinical benefit in heavily pre-treated pts with refractory HR+HER2- BC or TNBC. Clinical benefit was similar across the subgroups of pts with HR+ HER2-zero and HR+ HER2 low disease. Citation Format: Piha-Paul Sarina, Binghe Xu, Ying Fan, Yuan Yuan, Sayeh Lavasani, Joanne Mortimer, Sanjay Goel, Apostolia Tsimberidou, Nuhad Ibrahim, Sausan Abouharb, Carlos Barcenas, Adaeze lheme, Daniel Karp, Jordi Rodon Ahnert, Ecaterina Dumbrava, Jean Fan, Peng Peng, Caixia Sun, Hui Wang, Katie Hennessy, Ximei Fu, Ruolan Xu, Shumao Ni, Frank Wu, Funda Meric-Bernstam. The efficacy and safety of tinengotinib in patients with advanced or metastatic HR+/HER2- breast cancer or TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr RF01-07.

Abstract PS08-08: Updated efficacy and safety of SKB264 (MK-2870) for previously treated metastatic triple negative breast cancer (mTNBC) in Phase 2 study

Abstract Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The estimated median overall survival (OS) of pts with mTNBC is 12 to 18 months (mo) after diagnosis. SKB264, an antibody drug conjugate (ADC) composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan-derivative via a novel linker with an average Drug to Antibody Ratio (DAR) of 7.4, has shown promising anti-tumor activity and tolerable safety profile in pts with mTNBC (Yin, Y. et al. SABCS 2022). Here, we report the updated data from a Phase 2 expansion cohort for pts with mTNBC (NCT04152499). Methods: Pts with previously treated mTNBC were enrolled to receive SKB264 at 4 mg/kg Q2W or 5 mg/kg Q2W in a non-randomized manner until disease progression or unacceptable toxicity. Tumor assessment was performed every 8 weeks per RECIST v1.1 assessed by investigator. The primary objective was to assess objective response rate (ORR). Secondary objectives included DoR, PFS, and OS. The TROP2 expression was scored using the semi-quantitative H-score method, and a preliminary cutoff was set as 200. TROP2 expression and its association with anti-tumor activity were retrospectively analyzed. Results: At data cut-off date (May 05, 2023), 59 pts were enrolled (23 in 4 mg/kg, 36 in 5 mg/kg), and 88% (52 pts) had received ≥3 prior lines of therapy for metastatic disease. The median follow-up was 22.8 months (mo; 95% CI, 21.3-25.2). The ORR was 42.4% (25/59, 22 confirmed and 3 unconfirmed) and disease control rate (DCR) was 76.3% (45/59). The median duration of response (DoR) was 11.5 mo (range, 3.7 to 22.1+). Median PFS (mPFS) was 5.7 mo (95% Cl: 3.8, 9.1). Median OS (mOS) was 16.8 mo (95% Cl: 12.7, NE), while 12-mo and 24-mo OS rates were 65.0% and 39.5%, respectively. In the subset of pts with high TROP2 expression (H-score&amp;gt;200, N=32), ORR was 53.1% (including 3 complete response), mDoR was 11.1 mo (range, 3.7 to 22.1+), mPFS was 5.8 mo (95% Cl: 3.7, 13.3), mOS was not reached (95% Cl: 9.7, NE), while 12-mo and 24-mo OS rates were 65.3% and 57.3%, respectively. Treatment-related adverse events (TRAEs) of ≥ Grade 3 severity were reported in 57.6% (34/59) of pts. The most common ≥ Grade 3 TRAEs (≥ 10%) were neutrophil count decreased (25.4%), white blood cell count decreased (23.7%), anemia (22.0%) and platelet count decreased (16.9%). TRAEs leading to dose reduction and dose delay occurred in 13.6% (8/59) and 47.5% (28/59) of pts, respectively. Three pts discontinued treatment due to TRAEs (platelet count decreased, dry eye, anaphylactic shock). No cases of interstitial lung disease (ILD), neuropathy or grade ≥3 diarrhea were observed. Serious TRAEs were reported in 28.8% (17/59) of pts; no deaths associated with TRAEs were observed. Conclusions: The updated data continues to demonstrate that pts with heavily pretreated mTNBC could achieve durable response and a trend of long-term OS benefit from SKB264 treatment, along with a manageable safety profile. Higher response rate was seen in mTNBC pts with high TROP2 expression. A Phase 3 study of SKB264 vs. investigator’s choice of chemotherapy in 3L+ mTNBC (NCT05347134) and a Phase 2 study evaluating SKB264 as monotherapy or combination with anti-PD-L1 antibody in first-line setting (NCT05445908) are ongoing in China. Citation Format: Yongmei Yin, Xinhong Wu, Quchang Ouyang, Min Yan, Lihua Song, YunPeng Liu, Zhongsheng Tong, Cuizhi Geng, Ying Wang, Guohua Yu, Xiang Wang, Ying Cheng, Weihong Zhao, Xiaoping Jin, Yina Diao, Gesha Liu, Mengyu Yang, Yue Yang, Yalan Yang, Lian Lu, Junyou Ge, Jin Li, Qun Li. Updated efficacy and safety of SKB264 (MK-2870) for previously treated metastatic triple negative breast cancer (mTNBC) in Phase 2 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-08.

Abstract PO4-06-07: Efficacy and safety of futibatinib in patients with locally advanced/metastatic triple-negative breast cancer harboring FGFR2 gene amplification: final results from the phase 2, open-label FOENIX-MBC2 study

Abstract Background: Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancers and represents an aggressive subtype with limited targeted therapeutic options. Fibroblast growth factor receptor (FGFR) signaling plays an important role in breast tumorigenesis and metastasis. The phase 2 FOENIX-MBC2 study (NCT04024436) was designed to evaluate responses to futibatinib, a highly selective and potent irreversible covalent inhibitor of FGFR1–4 (FDA-approved for intrahepatic cholangiocarcinoma), in patients with metastatic breast cancer. Here, we report final efficacy and safety data for futibatinib in the cohort of patients with advanced/metastatic TNBC harboring FGFR2 gene amplification. Methods: Eligible patients had locally advanced/metastatic TNBC with measurable disease per RECIST v1.1, an ECOG performance status of 0/1, and progressive disease after ≥1 prior chemotherapy-containing regimen for advanced disease. Patients were positive for FGFR2 gene amplification determined by analysis of tumor tissue or circulating tumor DNA. Patients received oral futibatinib 20 mg once daily until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary endpoint was objective response rate (ORR) by RECIST v1.1 in patients with centrally confirmed FGFR2 amplification. Responses (complete response and partial response) required confirmation after at least 4 weeks. Secondary endpoints included the 6-month progression-free survival (PFS) rate, PFS, duration of response (DOR), and overall safety. Results: Overall, 21 female patients with TNBC were enrolled (median age: 53 years) in this cohort. Patients had received a median 5 lines of prior systemic therapy. Overall, 2 patients had a confirmed partial response (ORR: 9.5%; 95% confidence interval [CI]: 1.2, 30.4), with a median DOR of 6.1 months (range: 3.1−9.2 months). Five (23.8%) patients had stable disease. PFS at 6 months was observed in 4 patients (19.0%; 95% CI: 5.4, 41.9) and the median PFS was 1.9 months (95% CI: 1.6, 4.0). Twenty patients (95.2%) had ≥1 treatment-related adverse event (TRAE), including 7 (33.3%) with a Grade 3 TRAE (no Grade 4 or 5). Common TRAEs (any grade) included hyperphosphatemia (85.7% of patients), constipation, diarrhea, fatigue, and dry skin (each in 23.8% of patients). Anemia was the only Grade 3 TRAE observed in more than 1 patient (n=2, 9.5%). Overall, 28.6% of patients had a serious adverse event (SAE; any cause), and 1 patient had an SAE leading to death (ischemic stroke). None of the SAEs or deaths were considered treatment-related. Conclusions: In heavily pretreated patients with metastatic TNBC harboring FGFR2 gene amplification, futibatinib monotherapy demonstrated modest anticancer activity. Futibatinib was tolerable and had an acceptable safety profile, consistent with previous data. Further biomarker work to identify patients who might benefit most from futibatinib is ongoing. Clinical trial information: NCT04024436 Citation Format: Antonio Giordano, Nisha Unni, Senthil Damodaran, Hope Rugo, Timothy Crook, Thomas Bachelot, Federico Piacentini, Hector Soto Parra, Ian Krop, Masashi Shimura, Gareth Tomlinson, Maciej Gil, Nicholas Turner, Fabrice André. Efficacy and safety of futibatinib in patients with locally advanced/metastatic triple-negative breast cancer harboring FGFR2 gene amplification: final results from the phase 2, open-label FOENIX-MBC2 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-06-07.

Abstract PO2-27-01: TFX06, a next-generation oral CERAN/SERD, shows favorable safety and PK profile, extracranial and intracranial efficacy in patients with ER+/HER2- breast cancer: Preliminary results from a phase 1/2 first-in-human trial

Abstract Aims: TFX06 is an investigational oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) (Wu J, et al., 2023 AACR annual meeting). A Phase 1/2, multicenter, open-label dose-escalation and dose-expansion study (CTR20230789) was initiated in China to evaluate TFX06 in previously heavily treated patients with ER+/HER2- locally advanced and/or metastatic breast cancer. The primary objectives were to assess safety and tolerability, recommended Phase 2 dose (RP2D), and pharmacokinetics (PK). Methods: A 3+3 dose-escalation design was implemented. TFX06 tablets were orally administered at 60 mg/100 mg daily for 28 days of treatment cycle until disease progression or intolerant to TFX06. As of the cut-off date (Sept. 15, 2023), the Phase 1 study enrolled five patients with Stage IV diseases with distant metastases. Three were treated with TFX06 at 60 mg, the starting dose and two at the next dose level of 100 mg. Median age of patients were 50 years (39-65) with a ECOG score of 0-1. Two out of five patients carried estrogen receptor 1 (ESR1) mutations (ctDNA). Prior anticancer treatments included one or two lines of endocrine therapies, including fulvestrant, and/or one or two lines of chemotherapies. Clinical responses by investigator according to RECIST v1.1 were performed every two cycles to explore preliminary efficacy. Results: Three patients in 60 mg and one in 100 mg dose cohorts completed dose-limiting toxicity (DLT) observation period. No DLT observed. All treatment related adverse events (TRAEs) were grade 1-2 in severity, including nausea, drowsiness, decreases in WBC and neutrophils, and anemia. Analyses of plasma concentrations of TFX06 in all three patients receiving 60 mg revealed a similar PK profile with small variations in Cmax. The average steady-state Cmax and Cmin of TFX06 were 101 ng/mL and 65 ng/mL, respectively, and the Cmax of TFX06 was approximately 4-fold higher than that of fulvestrant administered intramuscularly at 500 mg in clinic (28 ng/mL). Two patients in the 60 mg cohort were evaluable for response assessment. One patient discontinued due to progressive disease (PD) after two cycles of treatment. This patient experienced a 17.1% decrease in target lesions in the lung; however, new metastases to bone observed. The other patient who carried ESR1 D538G mutation showed a decrease of 91% in ESR1 mutation burden 8 days after treatment, and a decrease of 34.2% in target lesions (partial response, PR), including a substantial shrinkage of 78.6% in the brain lesion (target lesion), as well as complete responses (CR) of non-target lesions in lung after 4 cycles of treatment. This patient remains on the study as of the cut-off date. Conclusions: Based on the preliminary results, oral administration of TFX06 at 60 or 100 mg once daily had favorable safety and PK profiles. TRAEs, such as gastrointestinal toxicities, bradycardia, and visual disturbances were not observed. Pleasingly, TFX06 demonstrated early extracranial and intracranial antitumor activity (PR) in a patient with a brain metastasis. Citation Format: Zhaojian Fu, Zhiye Zhang, Jia Song, Yang Chen, Douglas Fang, Wei Sha, Jian Zhang, Charles Ding. TFX06, a next-generation oral CERAN/SERD, shows favorable safety and PK profile, extracranial and intracranial efficacy in patients with ER+/HER2- breast cancer: Preliminary results from a phase 1/2 first-in-human trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-01.