Preliminary Efficacy Data Research Articles

Efficacy and safety of IBI110 in combination with sintilimab in first-line advanced HER2-negative gastric cancer or gastroesophageal junction cancer: Updated results from a phase Ib study.

2576 Background: Sintilimab plus oxaliplatin and capecitabine (XELOX) has become the standard of care in patients (pts) with untreated advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ AC) in China. Dual inhibition of PD-1 and lymphocyte-activation gene 3 (LAG-3) may further improve anti-tumor effect. The preliminary safety and efficacy data of IBI110 plus sintilimab and XELOX in pts with first-line G/GEJ AC were previously presented (Chenyu Mao et al. ASCO 2022). Here, we presented updated safety and efficacy results of this study. Methods: This phase Ib study enrolled patients with previously untreated, unresectable, locally advanced or recurrent/metastatic HER2-negative GC/GEJ AC. Pts received IBI110 200mg IV Q3W and sintilimab 200mg IV Q3W plus XELOX (oxaliplatin 130 mg/m2 Q3W and capecitabine 1000mg mg/m2/time twice daily [BID]) until disease progression, unacceptable toxicity or death. The primary objectives were to evaluate the safety, tolerability, and efficacy of the combination therapy per RECIST v1.1. Results: As of data cutoff January 9th 2023, 17 pts were assessed as evaluable (median age: 61 years; ECOG PS=1: 14 pts; all gastric cancer). All pts (17/17, 100%) experienced treatment-related adverse events (TRAEs) of any grade, and the most commonly TRAEs were neutrophil count decreased (64.7%), white blood cell count decreased (52.9%), platelet count decreased (52.9%). Grade ≥ 3 TRAEs occurred in 11 pts (64.7%), the most frequent grade ≥ 3 TRAEs were consistent with TRAEs of any grade. Investigator-assessed immune-mediated adverse events (irAEs) occurred in 10 pts (58.8%). Grade ≥ 3 irAEs occurred in 3 pts (17.6%), all led to discontinuation. No treatment-related death occurred. As data cutoff, among 17 efficacy-evaluable pts, the unconfirmed and confirmed objective response rate (ORR) were 88.2% (95% CI, 63.6-98.5) and 64.7% (95% CI, 38.3-85.8), respectively. The disease control rate (DCR) was 94.1% (95% CI, 71.3-99.9). With a median follow up of 13.1 months (95% CI, 7.1-NC), the median duration of response (DoR) and progression-free survival (PFS) were 11.6 months (95% CI, 2.5-14.4) and 12.9 months (95% CI, 3.8-15.8), respectively. The median overall survival (OS) was not reached, and the 12-months OS rate was 70.6% (95% CI, 43.1-86.6). Conclusions: IBI110 in combination with sintilimab and XELOX demonstrated manageable safety and encouraging efficacy results in patients with first-line gastric adenocarcinoma. This is the first positive trial to show clinical benefits of a LAG3 plus PD-1 inhibitor combined with chemotherapy for this population. Clinical trial information: NCT04085185 .

Phase 1 study of ziftomenib (KO-539) in combination with venetoclax or venetoclax/azacitidine or standard induction cytarabine/daunorubicin (7+3) chemotherapy for the treatment of patients with acute myeloid leukemia.

TPS7079 Background: Relapsed or refractory (R/R) acute myeloid leukemia (AML) with nucleophosmin 1-mutations ( NPM1-m) or KMT2A-rearrangment ( KMT2A-r) represent a high unmet need. Ziftomenib is a potent and selective inhibitor that targets the menin-mixed-lineage leukemia (MLL) lysine[K]-specific methyltransferase 2A ( KMT2A) interaction driving leukemogenesis in these subtypes. An ongoing Phase 1/2 study (KO-MEN 001) has demonstrated meaningful clinical activity and tolerability with ziftomenib monotherapy in R/R AML. In preclinical testing, ziftomenib combined with venetoclax induced synergistic lethality in KMT2A-r and NPM1-m human AML cell lines and patient-derived cells. Moreover, treatment with ziftomenib plus venetoclax/azacitidine has induced prolonged durable remissions in mice with KMT2A-r AML xenografts. Therefore, administration of ziftomenib in combination with standard-of-care (SOC) therapies may provide additional clinical benefit for patients with newly diagnosed or R/R NPM1-m and KMT2A-r menin-dependent AML. Methods: KOMET-007 (KO-MEN-007, NCT# ) is a 2-part dose escalation (Phase 1a) and expansion (Phase 1b) study to evaluate the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with non-intensive chemotherapy (NIC) and intensive chemotherapy (IC) in patients with NPM1-m and KMT2A-r AML. During Phase 1a, the ziftomenib dose will be escalated with standard doses of either venetoclax and azacitidine (zifto/ven/aza) or cytarabine and daunorubicin (zifto/7+3) in defined genetic cohorts ( NPM1-m and KMT2A-r) using a rule-based approach (n = 6 per cohort/dose level) to select ziftomenib doses for expansion/validation in Phase 1b. The Phase 1b portion will also evaluate zifto/ven/aza in newly diagnosed AML ( KMT2A-r and NPM1-m) and zifto/ven in R/R AML ( NPM1-m only). The overall primary objectives are to establish the minimum biologically effective, dose limiting toxicities, and recommended Phase 2 dose of ziftomenib combined with NIC and IC backbones in each genetically defined cohort. Additional secondary endpoints include preliminary antileukemic efficacy (including MRD-negative responses and number of patients able to transition to subsequent allogeneic stem cell transplant), pharmacokinetic, and pharmacodynamic data. Exploratory end points include biomarkers for efficacy and resistance, pharmacodynamic biomarkers and activity in isolated myeloid sarcoma. Clinical trial information: NCT04067336 .

A first-in-human study of CD123 NK cell engager SAR443579 in relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high-risk myelodysplasia.

7005 Background: SAR’579 is a trifunctional natural killer (NK) cell engager targeting CD123 antigen and co-engaging NKp46 and CD16a on NK-cells. SAR’579 facilitates the formation of a cytolytic synapse between NK-cells and CD123-positive tumor cells leading to NK-cell activation and tumor cell killing. We herein report preliminary safety and efficacy data of SAR’579 from a phase 1/2 trial in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia or high risk-myelodysplasia (NCT05086315). Methods: SAR’579 was administered intravenously twice weekly or once weekly (QW), depending on the dose level (DL) for the first 2 weeks of cycle 1 and then weekly for rest of induction cycles. A patient receives approximately three 28-day induction cycles with patients achieving a complete remission (CR) or incomplete hematologic recovery (CRi) per International Working Group criteria transitioning to a 56-day maintenance period with dosing approximately every 29 days. The primary objectives were to establish safety/tolerability and anti-leukemic activity (composite complete remission [CRc] = CR+CRi). Results: With a cutoff date of January 27, 2023, total 23 patients with R/R AML across 6 DLs (3 patients DL1 and 4 each in DL2 - DL6) were included in the safety population. The median age was 70 years (range: 21 - 80) with 9 patients (39.1%) reporting prior hematopoietic stem cell transplantation (HSCT) and 16 (69.6%) had prior exposure to venetoclax. Patients received a median of 2 cycles (range: 1 – 7) for median duration of 7 weeks (range: 1 - 25) and escalating doses of SAR’579 between 10 - 3000 µg/kg/dose in cycle 1 and 100 - 3000 µg/kg QW for the rest of induction cycles. No dose limiting toxicities (DLTs) were observed among the 21 DLT-evaluable patients, until highest dose of 3000 µg/kg QW. The most common treatment emergent adverse events (TEAEs) included infusion-related reactions (n = 10 [43.5%]) and nausea (n = 7 [30.4%]). TEAEs were reported in 22 patients (95.7%) with grade 3/4 adverse events (AEs) in 18 (78.3%) and treatment-related AEs in 16 patients (69.6%), respectively. There were 2 cases of cytokine release syndrome (n = 1 grade 1 and n = 1 grade 2) and no case of immune effector cell-associated neurotoxicity syndrome. No patient reported TEAE leading to permanent discontinuation of SAR’579. The CRc rate was 13.0% (3/23 patients evaluable for response). In DLs with a highest dose of 1000 µg/kg QW, 3/8 (37.5%) patients achieved a CR (2 CR/1 CRi). The median time to first CR/CRi was 16.1 weeks 95% confidence interval (8.1 – Not Estimable [NE]), and the median duration of CR/CRi is NE due to limited follow-up time. Conclusions: SAR’579 was well tolerated up to doses of 3000 µg/kg QW with observed clinical benefit in patients with R/R AML. The trial continues to accrue patients. Clinical trial information: NCT05086315 .

Phase 1b study of HS-10241 combined with almonertinib in pre-treated advanced non-small cell lung cancer (NSCLC) harboring EGFR mutation.

e21134 Background: MET gene amplification is one of the most frequent acquired resistance mechanisms following prior EGFR-TKI monotherapy. HS-10241, an oral and highly selective MET-TKI, may contribute to overcoming common acquired MET-based resistance mechanisms. Here, we reported the preliminary safety and efficacy data of HS-10241 with almonertinib in treatment of advanced NSCLC with EGFR mutation. Methods: This Ph1b study (NCT05430386) was composed of dose escalation part (Part 1) and dose expansion part (Part 2). In Part 1, patients (pts) with EGFR-mutated advanced NSCLC upon disease progression on EGFR-TKI received HS-10241 (BID) plus almonertinib (110 mg QD), and HS-10241 was escalated at 200 mg and 300 mg using a rolling six design. Based on the available data of Part 1, an expansion cohort was opened at HS-10241 300 mg BID with almonertinib 110mg QD to enroll pts with EGFR mutation centrally confirmed and MET-amplification detected by central FISH (MET gene copy number[GCN] ≥5 and/or MET:CEP7 signal ratio ≥2). Results: As of 16 December 2022, 10 pts in part 1, 4 pts at 200 mg and 6 pts at 300 mg HS-10241, and 35 pts in part 2 were enrolled into this study. Of these pts, 13 (28.9%) pts received previous treatment with 1st or 2nd-generation but no 3rd-generation EGFR TKI, 15 (33.3%) pts received 3rd-generation EGFR-TKI only and 15 (33.3%) pts received both 1st/2nd and 3rd-generation EGFR TKIs, whether or not they received treatment with chemotherapy. Only one dose-limiting toxicity (grade 2 Nausea with grade 2 vomiting leading to discontinuation≥14 days) was reported in the cohort with HS-10241 300 mg. The MTD was not reached. Treatment-emergent adverse events (TEAEs) occurred in 41/45 (91.1%) pts. The most common TEAEs (≥ 20%) were increased AST, increased ALT, vomiting, nausea, increased blood creatine phosphokinase, thrombocytopenia, decreased appetite, and increased GGT. Among all the pts, 22 pts with EGFR mutation regardless of the MET gene status were evaluable for efficacy, 12 of which achieved partial response (response rate 54.5%; 8 confirmed PR), and 7 had stable disease (SD). Of the 13 pts who had centrally confirmed EGFR mutation and MET-amplification (6 with GCN ≥10, and 7 with GCN ≥5 but < 10), 8 had PR (response rate 61.5%; 5 confirmed PR), and 4 had SD. Among the 8 pts achieving PR, there were 4 with GCN ≥10, and 4 with GCN ≥5 but < 10.Moreover, 9 of the 13 pts received both 1st/2nd and 3rd-generation EGFR-TKI and there were 6 PRs (response rate 66.7%;3 confirmed PR) and 2 SDs. Pharmacokinetics analysis showed low risk of potential drug-drug interactions on HS-10241 combined with almonertinib. Conclusions: HS-10241 in combination with almonertinib was well tolerated, and showed encouraging antitumor activity in treatment of advanced NSCLC with EGFR mutation and MET amplification following prior EGFR-TKI, whether MET GCN ≥10 or MET GCN ≥5 but < 10. Clinical trial information: NCT05430386 .

Preliminary results of a phase 1, first-in-human study of INA03, an anti-CD71 antibody-drug conjugate, in patients with relapsed or refractory (R/R) acute leukemias.

7045 Background: R/R acute leukemias (AL) represent major therapeutic challenges. Several reports have highlighted the role of iron metabolism in various proliferative tumor models including AL including the over-expression of the transferrin receptor (TfR1/CD71). Our strategy is thus to harness CD71 overexpression to specifically target cytotoxic agents to leukemic cells. INA03 is an antibody drug conjugate (ADC) constituted of a humanized monoclonal IgG4 against CD71 and the microtubule disrupting agent monomethyl auristatin E (MMAE). We herein report the preliminary safety and efficacy data of INA03 from a phase 1/2 trial in patients (pts) with R/R AL (NCT03957915). Methods: INA03 is given as 30 minutes IV infusion on days 1 (Loading dose (LD)) followed by maintenance injections on D15 for cycle 1 and on D1 and D15 of cycle 2 and beyond. Eligibility criteria are: R/R AL after at least one line of treatment including high dose chemotherapy and/or Vidaza and Venetoclax, AlloSCT > 18y, with FEVG > 50%, Creatinine Clearance > 30ml/min, normal liver function, ECOG < 2. The study design is based on a continuous reassessment method and includes 2 parts: a LD Titration study (Part 1, completed), followed by a Dose Escalation Part 2. During Part 1, sequential cohorts of 2 pts were included to receive ascending LD of INA03 followed by subsequent fixed dose of INA03 to deal with a potential sink effect related to the high expression of CD71 in normal erythroblasts. During Part 2, sequential cohorts of 3 pts received escalating doses of INA03 Q2 weeks in 28-day cycles. The objectives were to establish the MTD for subsequent administration and both safety/tolerability and anti-leukemic activity. Results: With a cutoff date of January 18, 2023, 22 pts across 8 cohorts were included in the study. The median age was 73 (range: 39 – 83), 20 (91%) pts had AML and two (9%) had ALL. Three (13.6%) pts had a prior allo-SCT and 12 (54.5%) had prior VEN exposure. Pts received escalating doses of INA03 of 0.02 mg/kg to 2 mg/kg. MMAE pharmacokinetics (PK) appears dose-proportional with a small accumulation after repeated IV, while INA03 PK exhibits target-mediated drug disposition without accumulation. No DLT was observed among the 18 DLT-evaluable pts, up to the highest dose of 2 mg/kg. No grade 2-4 TEAEs were observed. One related grade 1 TEAE (hyperkalemia/phosphatemia) was reported. Transient decrease of reticulocyte count and erythroblasts percentage were observed at 0.5 mg/kg and above. Blasts reductions were seen in 3/18 evaluable pts at dose > 1 mg/kg including two partial responses. Conclusions: INA03 is well tolerated up to the dose of 2 mg/kg with some efficacy signals in R/R AL. The trial continues to accrue patients. Clinical trial information: NCT03957915 .

OMNIA-1: A phase I/II study, an IL-2R-βγ targeted antibody-IL-2 fusion protein, as monotherapy or in combination with anti-PD-1 or anti-CTLA-4 antibodies, in patients with advanced melanoma.

TPS9599 Background: ANV419 is a potent and selective IL-2Rβγ targeted antibody IL-2 fusion protein, designed to enable the delivery of high dose interleukin-2 (IL-2) to patients in order to stimulate anti-tumour response and minimise toxicities. Recombinant IL-2 (proleukin) induces durable responses in approximately 10% of patients with melanoma. Signalling through IL-2Rα expressing cells is believed to limit its therapeutic potential in cancer. By eliminating binding to IL-2Rα, ANV419 could lead to increased anti-tumor effect while increasing tolerability. The ANV419-001 first-in-human study (NCT 04855929) demonstrated that ANV419 preferentially stimulates cytotoxic CD8+ T and natural killer (NK) cells over immunosuppressive regulatory T cells, with a significantly longer half-life than that of conventional IL-2. The safety and tolerability data from this study confirmed that ANV419 delivers high molar equivalents of IL-2 in a tolerable and convenient way. Methods: ANV419 is being evaluated in a global multicentre, open-label, randomized Phase I/II study in patients with unresectable or metastatic cutaneous melanoma to assess the safety and efficacy of intravenous ANV419 as monotherapy and in combination with anti-PD1 or anti-CTLA-4 antibodies. The OMNIA-1 study leads in with a monotherapy dose expansion part, followed by a combination dose-finding with either anti-PD-1 or anti-CTLA-4 and a combination dose expansion part. ANV419 is administered intravenously every 2 weeks as monotherapy and every 3 weeks when given in combination. Patients with advanced cutaneous melanoma, no active brain metastases and whose disease has progressed on or following at least 1 line of standard of care immunotherapy are eligible. In Part 1, a total of 30 patients will be randomised and evaluated for response to Q2W ANV419 monotherapy (108 µg/kg or 243 µg/kg). In Part 2, escalating doses of Q3W ANV419 are evaluated to define the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) in combination with pembrolizumab (200 mg) or ipilimumab (3 mg/kg). In Part 3, the efficacy and safety of ANV419 in combination with the approved doses pembrolizumab or ipilimumab will be evaluated using a Simon’s 2-stage design. Up to 130 patients are planned to be enrolled. Patients will be stratified according to BRAF mutation status. AEs are assessed according to CTCAE V5.0. Tumour response is determined using RECIST 1.1 criteria. The study is conducted at sites in the US, France, Spain, Germany, Italy, and UK. The first patient was dosed in December 2022. Preliminary monotherapy efficacy data are expected by Q1/2024. Clinical trial information: NCT05578872 .

Safety and efficacy of HB0025, an anti-PD-1/VEGF bispecific antibody fusion protein, in patients with advanced solid tumors: Preliminary results from an FIH trial.

2589 Background: HB0025 is a recombinant humanized anti-PD-L1 monoclonal antibody-VEGFR1 fusion Protein. Nonclinical data both in vitro and vivo have shown high-affinity binding to both targets as well as the inhibition of tumor growth in animal models. Here, we present preliminary safety and efficacy data from a dose escalation phase I study of HB0025. Methods: Eligible patients(pts) were ≥18 years old (ECOG PS 0–1) who had advanced solid tumors (NSCLC, gynecological tumors, digestive system tumors, etc.) and failed standard treatment. This phase 1 dose escalation includes accelerated titration (0.01, 0.03, 0.1 and 0.3mg/kg) and conventional 3+3 dose escalation (1.0, 3.0, 6.0, 10, 12, 20, and 30.0 mg/kg). HB0025 is administered intravenously every 14 days (Q2W). Objectives include evaluation of safety, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and antitumor activity. Adverse events (AEs) were reported with CTCAE v5.0 and DLTs were evaluated within a 28-day window. Results: As of Aug 30th 2022, 30 pts including 8 male and 22 female from Caucasian and Mongoloid have received HB0025 at doses of 0.01 mg/kg (n=1), 0.03 mg/kg (n=2), 0.1 mg/kg (n=1), 0.3 mg/kg (n=1),1.0 mg/kg (n=3), 3.0 mg/kg (n=7), 6.0mg/kg (n=7), 10.0 mg/kg (n=5), and 12.0mg/kg (n=3) Q2W. Overall, the median age was 55 years and the median lines of previous treatment was four. Of the 22 evaluable pts dosed at ≥ 3 mg/kg Q2W, the ORR was 9.1% (2/22) and the disease control rate (DCR) was 50% [11/22]. Among the 2 responders, a CR (colorectal ca) pt whose prior therapy was no immune checkpoint inhibitor (ICI) or bevacizumab have continued more than 36 weeks; and a PR (NSCLC) pt with duration more than 18 weeks whose tumor was 60.2% regression and prior ICI failure. Till the date of submission, the therapy was continuing for the CR and PR pts. Treatment-related adverse events (TRAEs) occurred in 83.3% of pts. The grade 3 TRAEs occurred in 20% [6/30] and treatment-related SAEs occurred in 13.3% [4/30]. One DLT occurred in the 12.0mg/kg cohort. No death occurred related to HB0025. TRAEs leading to treatment discontinuation occurred in 13.3% of pts [4/30]. The most frequent TRAEs were hypertriglyceridemia (23.3%), hypercholesterolemia (23.3%), anemia (16.7%), alanine aminotransferase increase (16.7%), and proteinuria (13.3%). Conclusions: HB0025 shows manageable safety and promising anti-tumor activity in pts with various solid tumors. To better characterize the risk-benefit profile, HB0025 is currently enrolled at 20.0 mg/kg Q2W and is being explored at doses 10 mg/kg in expansion cohorts. The future data, including PK, PD and ADA will be presented. Clinical trial information: NCT04678908 .

First-in-human, phase 1a dose finding of LVGN6051 CD137/4-1BB agonistic antibody with or without pembrolizumab in patients with advanced solid tumors.

2525 Background: LVGN6051 is a conditional 4-1BB agonistic monoclonal antibody with Fc γ-receptor IIB selective binding in the tumor microenvironment for optimal activity. Preclinical studies showed potent antitumor activity by LVGN6051 alone and in combination with anti-PD-1 antibody. Methods: We conducted this first in human (FIH) multicenter phase 1 dose escalation study in the US. Eligible pts with advanced solid tumor malignancies received escalating doses of LVGN6051 alone or in combination with pembrolizumab 200 mg IV Q3W until unacceptable toxicity, progressive disease, or withdrawal of consent. Results: As of Jan 23, 2023, 55 pts were enrolled and received LVGN6051 alone with the dose range of 0.003–7 mg/kg (n=18), or combination therapy of LVGN6051 2 mg/kg + pembrolizumab (n=22) or LVGN6051 4 mg/kg + pembrolizumab (n=15). The median age was 58 years (range 20-83) and number of prior therapies was 5; 46 pts (84%) had ECOG PS 1 and 21 pts (38%) had received prior immune checkpoint inhibitors (ICI). In pts who received LVGN6051 alone, the MTD was not reached up to 7 mg/kg and the RP2D was selected as 4 mg/kg IV Q3W for tolerance. The RP2D for combination therapy was established as LVGN6051 4 mg/kg and pembrolizumab 200 mg IV Q3W. Pts received a median of 2.8 months and a mean of 4.0 months (range 0.5 – 19.2) of study treatment. 33 pts (60%) experienced any grade treatment-related adverse events (TRAEs) with noteworthy (> 5%) AST increased (27%), ALT increased (26%), thrombocytopenia (16%), infusion related reaction (IRR) (9%), fatigue (7%), lipase increased (6%), nausea (6%) and chills (6%). 14 pts (25%), 1 mono- and 13 combination therapy, showed ≥ grade 3 TRAEs: AST increased (11%), ALT increased (9%), thrombocytopenia (7%), fatigue (4%), IRR (2%), lipase increased (2%) and nausea (2%). 6 drug-related serious adverse events and 1 DLT (grade 4 thrombocytopenia), all in combination therapy, were reported. In 42 evaluable pts, the disease control rate (DCR) was 50%. Combination therapy showed that target lesions were reduced by 57%, 42% and 48% in melanoma (n=2) and pancreatic cancer (n=1), respectively. Among 11 melanoma pts (10 had progressed on anti-CTLA4 and anti-PD-1 therapy), 2 PR and 5 SD were observed per RECIST 1.1, including one being treated for 19+ months (26+ cycles). Pts with HNSqCC (n=1) and CRPC (n=1) also showed remarkable tumor shrinkage. Paired tumor biopsies for single cell RNAseq biomarker exploration confirmed activation of effector T cells following LVGN6051 treatment. Conclusions: We established the RP2Ds of LVGN6051 alone and in combination with pembrolizumab in this FIH phase 1a study. These regimens were well tolerated. Preliminary efficacy data showed encouraging anti-tumor activity in heavily pretreated pts who had progressed on ICI. Phase 1b dose expansion for the combination therapy is ongoing in pts with melanoma, GI malignancies and NSCLC. Clinical trial information: NCT04130542 .

Exploratory study investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20).

TPS12151 Background: In opioid therapy for cancer pain, it is essential to manage opioid-related adverse effects. Opioid-induced nausea and vomiting (OINV) is common, occurring in 20–40% of patients during initial opioid treatment or after opioid doses are increased. Tolerance to OINV develops within a few days to a week. In patients with cancer, OINV results in decreased quality of life as well as failure to relieve pain due to poor opioid adherence, thus increasing the psychological barriers to opioid use. Therefore, antiemetics are used for OINV prophylaxis, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapy, and it is less likely to cause extrapyramidal symptoms than haloperidol and prochlorperazine. We are conducting this exploratory study to evaluate the efficacy and safety of olanzapine prophylaxis against OINV. Methods: This single-arm, single-center exploratory study will evaluate the prophylactic antiemetic efficacy and safety of olanzapine (5 mg PO once a day for 5 days) in patients with cancer pain reserving initial regular opioid therapy. Thirty-five patients will be enrolled. This study was designed to provide preliminary efficacy data, with a primary objective of assessing the proportion of patients who achieved complete control (CC) of OINV during 120 hours of opioid treatment. CC was defined as the absence of emetic episodes, the lack of a need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the following: the complete response (CR) rate, defined as the percentage of patients with no emetic episodes and no rescue medication use; the total control (TC) rate, defined as the percentage of patients with no emetic episodes, no rescue medication use, and no nausea during the 120 hours of opioid treatment; the time from opioid initiation to the first emetic episode; the time from opioid initiation to the first administration of a rescue antiemetic; the time to treatment failure, defined as the time from opioid initiation to the first emetic episode or to the administration of a rescue antiemetic; the number of emetic episodes; the levels of nausea, anorexia, sleepiness, pain, and fatigue, all determined using a numerical rating scale (0–10); the impact of antiemetic therapy on daily life severity and patient satisfaction, determined using a 7-grade categorical scale; and adverse events graded by PRO-CTCAE ver.1.0 and CTCAE ver. 5.0. The study is currently open, and 25 patients have been enrolled at time of abstract submission. Clinical trial information: jRCTs031220008 .

Neoadjuvant single-dose trilaciclib prior to combination chemotherapy in patients with early triple-negative breast cancer: Safety, efficacy, and immune correlate data from a phase 2 study.

603 Background: Trilaciclib, an intravenous CDK4/6 inhibitor, induces transient G1 cell cycle arrest. In preclinical studies, trilaciclib demonstrated immune-modulating effects by enhancing T-cell activation, favorably altering the tumor microenvironment (TME), and improving long-term immune surveillance. Preliminary data from this phase 2, single-arm, open-label study of neoadjuvant trilaciclib in triple-negative breast cancer (TNBC; NCT05112536) showed that single-dose trilaciclib increased CD8+ T-cell/Treg ratios within the TME. Here, we combine immune analysis with clinical outcomes to identify correlates of treatment response. Methods: Patients (pts) with early-stage TNBC received single-dose trilaciclib followed by trilaciclib + dose-dense anthracycline/cyclophosphamide and taxane (AC/T). Per investigator discretion, pts received pembrolizumab (pembro) 400 mg Q6W from cycle 1 and/or carboplatin (carbo) AUC 1.5 QW from cycle 5. Tumor biopsies and blood samples were collected prior to treatment, 7 days post single-dose trilaciclib, and during surgery, with an additional blood sample at cycle 2. PDL1 status was assessed per Ventana SP142 assay (positive immune cell score ≥ 1%). The primary objective is to evaluate the immune-based mechanism of action of single-dose trilaciclib. Results: As of January 3, 2023, 18/24 pts had completed treatment and/or had definitive surgery; 1 pt with neuroendocrine features discontinued due to disease progression. Median age was 57 years. At diagnosis, 79% of pts had stage II tumors (88% with ductal carcinoma; 38% with PDL1+ tumors). 18 pts received pembro + carbo, 3 pts pembro only, and 3 pts carbo only. Common treatment-related adverse events (TRAEs) were fatigue (79%), nausea, (67%), alopecia (67%), and neutropenia events (63%); 42% of pts had grade 3/4 neutropenia events. 4 serious TRAEs occurred in 2 (8%) pts: pembro-related colitis and hypertransaminasemia, trilaciclib/paclitaxel-related urosepsis, and AC-related febrile neutropenia. Response data were available for 15 pts; pathologic complete response (pCR) was observed in 7 (47%) pts, with pCR rates of 86% vs 13% for pts with PDL1+ vs PDL1– tumors, respectively. Immune analysis of the TME post trilaciclib monotherapy demonstrated several pCR-related features, such as increased stromal tumor-infiltrating lymphocytes and granzyme B+ cells. Correlative blood analysis revealed increased circulating baseline CD8+ T cells in pts achieving pCR. Conclusions: Safety and tolerability data are encouraging for trilaciclib in combination with AC/T ± pembrolizumab ± carboplatin in the neoadjuvant setting for early-stage TNBC. Preliminary efficacy data align with standard neoadjuvant chemotherapy regimens. Final pCR data from all pts and immune correlates from tumor and blood samples will be presented. Clinical trial information: NCT05112536 .

A phase 1, multicenter, open-label study of a new BRAF inhibitor ABM-1310 in adult patients (pts) with BRAFv600-mutated solid tumors.

3098 Background: ABM-1310 is a novel small-molecule BRAF inhibitor with high water solubility, cell permeability, and blood-brain barrier penetration as demonstrated in preclinical studies. Here we report preliminary findings from a first-in-patient phase 1 study of ABM-1310. Methods: This US multicenter, open-label, dose-escalation with cohort expansion trial includes adult pts with advanced BRAFv600-mutated solid tumors, including those with active brain metastasis from solid tumors or primary malignant brain tumors. Previous BRAF/MEK inhibitor treatment is permitted. In dose escalation Part A, ABM-1310 monotherapy is given orally twice a day (25–250 mg bid). In dose escalation Part B, ABM-1310 (100 and 200 mg bid) is given in combination with the MEK inhibitor cobimetinib (60 mg QD d1–21 q4w). Primary objectives: determine maximum tolerated dose and recommended phase 2 dose of ABM-1310 ± cobimetinib. Secondary objectives: safety/tolerability; pharmacokinetics; preliminary efficacy. Dose-limiting toxicities (DLTs) are assessed during cycle 1 by a 3+3 design. Results: As of November 28, 2022, 20 pts (65% male; median age 57.5 years) have been treated with ABM-1310 monotherapy across six dose levels in Part A: 25 mg bid (n=3); 50 mg bid (n=3); 100 mg bid (n=4); 150 mg bid (n=4); 200 mg bid (n=4); 250 mg bid (n=2). All pts experienced adverse events (AEs), most frequently skin rash (40%) and QT prolongation (20%). Three pts had drug-related grade ≥3 AEs (nausea/vomiting, QT prolongation and rash) and two had drug-related serious AEs (SAEs) (nausea/vomiting and creatinine increase). Among 16 efficacy evaluable pts, two (pleomorphic xanthoastrocytoma and glioblastoma) had a partial response (PR) and eight had stable disease (SD) as their best response (per RECIST or RANO). In Part B, two ABM-1310 dose levels were assessed in combination with cobimetinib: 100 mg bid (n=3) and 200 mg bid (n=3). Four pts had AEs and drug-related AEs (rash and QT prolongation). There were no SAEs. Among three evaluable pts, one (melanoma) had a PR and one had SD as their best response. There were no confirmed DLTs in either dose-escalation Part A or B, although a few pts had ABM-1310 treatment interruption and subsequent dose reduction. No pts discontinued prematurely for any safety or tolerability reason and there were no drug-related deaths. Preliminary assessment of ABM-1310 drug exposure vs dosage showed a linear dose-proportional relationship. This trial is ongoing. Conclusions: ABM-1310 at the currently tested doses up to 200 mg bid, either alone or in combination with cobimetinib, was generally well tolerated, with no new safety signals. Preliminary efficacy data demonstrate favorable activity of ABM-1310 in pts with BRAFv600-mutated solid tumors, including primary CNS tumors, and pts previously refractory to other BRAF/MEK inhibitors and I/O therapies. Clinical trial information: NCT04190628 .

A phase 1 study of concurrent cabozantinib and cetuximab in recurrent or metastatic head and neck squamous cell cancer.

6025 Background: Epidermal growth factor receptor (EGFR) targeting with cetuximab (CTX) is a standard therapy for head and neck squamous cell carcinoma (HNSCC). Resistance to CTX can be mediated by activation of the receptor tyrosine kinase AXL. Cabozantinib (cabo) is a tyrosine kinase inhibitor (TKI) of AXL/c-MET/VEGFR which demonstrated antitumor activity in HNSCC preclinical models. We conducted a phase I trial to assess the safety and efficacy of the cabo-CTX combination in recurrent or metastatic (R/M) HNSCC. Methods: Eligibility criteria included RECIST v1.1 measurable disease and incurable R/M HNSCC. Prior treatment with CTX was allowed. Patients received an initial CTX loading dose of 400 mg/m2 followed by 250 mg/m2 weekly. CTX maintenance dose was later amended to 500 mg/m2 biweekly. Cabo was given concurrently on days 1-28 of each 28-day cycle. Primary endpoint was maximally tolerated dose (MTD) of cabo, as identified using a 3+3 dose-escalation design. Tumor responses were assessed every 2 cycles. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: Of 22 patients enrolled between 2018 and 2022, 2 did not start therapy. Among treated patients, median age was 59 (range 33-71) and 90% (n = 18) of patients were male. Primary tumor sites included the oropharynx (n = 13), oral cavity (n = 3), larynx (n = 2), hypopharynx (n = 1) and unknown primary (n = 1). p16 antigenic testing for HPV status was positive in 11 oropharyngeal cancers (85%). Most patients were previously treated with immune checkpoint inhibitors (n = 19), chemotherapy (n = 19), CTX (n = 16), or other TKI (n = 2). 12 patients received biweekly CTX dosing at 500 mg/m2. Initial cabo dose was 40 mg for the first 11 patients, and 60 mg afterwards (MTD). No dose-limiting toxicity (DLT) was recorded. Common adverse events (AEs) included fatigue (80%), acneiform rash (75%), increased aspartate aminotransferase (AST) (70%), anemia (70%) and hypothyroidism (70%). Grade ≥3 AEs occurred in 65% (n = 13), including increased AST (45%), increased alkaline phosphatase (15%), increased bilirubin (10%) and erythrodysesthesia (10%). AEs led to dose reductions in 20% (n = 4) and treatment discontinuation in 15% (n = 3). In the preliminary efficacy analysis, 4 patients had partial responses (PRs) with an ORR of 20%, including 2 PRs in patients with prior CTX resistance. Disease control rate (DCR) was 75% in the overall population and 75% in those with previous CTX treatment. Median PFS was 3.4 mo and median OS was 8.1 mo. PFS differed according to HPV status, with median PFS 7.1 mo versus 3.1 mo in HPV-positive and -negative patients respectively (p = 0.03). Conclusions: The cabo and CTX combination showed an acceptable toxicity profile with liver toxicity as a common AE. The regimen showed preliminary efficacy data in patients with R/M HNSCC, including those with prior CTX resistance. Clinical trial information: NCT03667482 .

EpCAM CAR T (IMC001) for the treatment of advanced GI cancers.

4034 Background: EpCAM is highly expressed in various cancer types of the GI system and at metastatic sites. It serves as a promising prognostic/predictive marker (CTC) and therapeutic target. IMC001 is an EpCAM-targeted CAR-T cell that showed promising anti-tumor activities in preclinical studies. Here, we report the results of the low and middle dosage groups in advanced gastric cancers (CT03) and GI cancers (CT04). Methods: This first-in-human, open-label trial involved two separate single-site trials. Both followed a classic 3+3 design with dose escalation of 0.3, 1 or 3 million CAR-T cells/kg after lymphodepletion chemotherapy. CT03 was an IMC001 monotherapy trial (Stage 1) for gastric cancer, while CT04 had Stage 1 and the combination with RFA or microwave ablation (Stage 2) for GI cancers. Eligible patients were those with EpCAM-positive (more than 10%) cancers who had no further standard treatment options and were ECOG 0 or 1. The objective was to assess the safety, PK/PD profile and preliminary efficacy of IMC001. Results: As of January 30, 2023, 12 patients with 6 colorectal and 6 gastric cancers had enrolled, with half receiving 0.3 million and the other half receiving 1 million cells/kg IMC001 infusion. No patient experienced DLT within the 4-week follow-up visits after infusion. All patients experienced ≥Grade 3 hematologic toxicity. One patient in the low-dose group had a SAE of immune hepatitis (Grade 3), which might have been related to cell therapy, and occurred around 11 days after the CAR-T infusion, prolonging the patient's hospitalization. Manageable CRS (Grade 1 to 3) and no ICANS were observed. Other adverse events related to cell therapy were CTCAE Stage 1-2 nausea, vomiting, asthenia, or pruritus, and these recovered quickly. Analyses of the CAR-T cells in peripheral blood revealed robust engraftment in all patients, with the peak number of CAR+ cells reaching on day 5-7 after infusion. CTC remained under the detection limit for more than 40 weeks after cell infusion. Significant elevations of serum levels of IL-6, IP-10, IFN-γ, IL-15, and MCP-1 were observed in most patients. Preliminary efficacy data showed that 2 out of 6 advanced gastric cancer patients were evaluated as PR and 3 remained SD by RECIST 1.1 at the low and middle dosages (CT03). The first PR patient received a second IMC001 infusion on week 50 and had survived for more than 60 weeks. The second PR patient underwent successful surgical removal of the stomach 28 weeks after IMC001 infusion. The CT04 trial is ongoing. Conclusions: This is the first CAR-T therapy ever tested in humans targeting the EpCAM. IMC001 showed a favorable safety profile and reasonable anti-tumor activities at the low and middle dosage levels in patients with advanced EpCAM+ GI cancers, especially in gastric cancer. In addition, our trial has successfully provided a surgical treatment opportunity after CAR-T therapy downstaging of unresectable gastric cancers. Updated data from open cohorts will be presented. Clinical trial information: NCT05028933 .

206P Capivasertib (C) + palbociclib (P) and fulvestrant (F) in patients (pts) with HR+/HER2- advanced breast cancer (ABC): Phase Ib data from CAPItello-292

AKT pathway activation is implicated in resistance to endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in pts with HR+/HER2– ABC. In CAPItello-291, C+F significantly improved progression-free survival vs F in pts with aromatase inhibitor-resistant HR+/HER2– ABC (HR 0.60; 95% CI 0.51–0.71; p<0.001) and pts with AKT pathway-altered tumours (HR 0.50; 95% CI 0.38–0.65; p<0.001). Simultaneous inhibition of AKT and CDK4/6 pathways may improve clinical outcomes by resensitising tumours to ET and CDK4/6i. This phase Ib/III study is evaluating the safety/efficacy of C+P+F vs placebo+P+F in HR+/HER2− ABC. Phase Ib used a Keyboard design (mTPI-2), and pts received C (320mg [C320] or 400mg [C400] twice daily, 4 days on/3 days off), P (100mg [P100] or 125mg [P125] once daily for 21 days of each 28-day cycle) and F (500mg [F500] every 28 days + loading dose on cycle 1 day 15); prior CDK4/6i was permitted. Phase Ib primary endpoints: safety/tolerability; confirmation of recommended phase III dose (RP3D). Serial ctDNA monitoring was performed and C/P pharmacokinetics were evaluated. Data cut-off: 31 Oct 2022. In 39 heavily pre-treated (median prior chemotherapies: 2 [range 0–8]) pts with a median age of 59 years (range 38–82), 7 dose-limiting toxicities (DLTs; mainly neutropenia related) were seen in 6 pts across doses and did not prevent escalation/expansion. C400+P125+F500 (n=12) was identified as the RP3D (1 DLT; Grade [G] 3 neutropenia). Most common adverse events were diarrhoea (69%; 1/27 G3), neutropenia (54%; 19/21 G≥3), fatigue and nausea (both 41%; all G1/2). No treatment-related deaths or new safety risks were identified. Preliminary efficacy and ctDNA data from pts treated at the RP3D will be presented. No clinically relevant drug–drug interaction was observed. C+P+F was tolerable in heavily pre-treated pts with HR+/HER2− ABC, with no marked safety differences among dose levels. DLTs were consistent with the expected safety profile.

Early clinical experience with cladribine tablets in a Black/Hispanic patient population (P9-3.001)

<h3>Objective:</h3> To report our early experience using cladribine tablets in a real-world US cohort of MS patients and of a subgroup who were Black/Hispanic. Outcomes presented include patient characteristics, previous DMT use, safety, and lymphocyte counts of both groups. <h3>Background:</h3> The efficacy and safety of cladribine tablets 3.5 mg/kg was demonstrated in clinical trials; however, the real-world clinical experience is still emerging. An area of growing interest is the use of disease-modifying therapies (DMTs) in racial minorities with multiple sclerosis (MS) as they have distinct disease characteristics but historically low participation in clinical trials. Understanding the risk/benefit profile of this therapy in these populations are of extreme importance. <h3>Design/Methods:</h3> Prospective and retrospective chart review of 72 patients with RMS who were treated with ≥1 course of cladribine tablets. A subgroup analysis was also performed for patients who were Black/Hispanic (n=26) <h3>Results:</h3> We report on 72 patients who have initiated therapy with cladribine tablets by data cut-off (June 2021). Median age at cladribine tablets initiation was 46 years (range 24–71) and 36% of patients were Black/Hispanic. Median disease duration was 13 years (range 2–34) and median baseline EDSS was 3.5 (range 0–7.5). The mean number of prior DMTs was 2.5 and 31% of patients completed both treatment courses by data cut-off. Overall, cladribine tablets were well tolerated. 57% of patients experienced lymphopenia with no grade 4 reported. No serious adverse events occurred. Updated data including preliminary efficacy data will be presented. <h3>Conclusions:</h3> In this cohort of patients initiating cladribine tablets in the real-world, the initial treatment was well-tolerated, even among those who are Black/Hispanic. The side effect profile was consistent with that seen in the clinical trial program. Ongoing follow-up will further expand on these results as more patients complete their full treatment course. <b>Disclosure:</b> Dr. Gutierrez has nothing to disclose. Dr. Ochoa has nothing to disclose.

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BackgroundIsolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues.MethodsROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment.DiscussionROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy.Trial registrationNCT05230251 (ClinicalTrials.gov).

LBA02-03 FIRST RESULTS FROM SunRISE-1 IN PATIENTS WITH BCG UNRESPONSIVE HIGH-RISK NON–MUSCLE-INVASIVE BLADDER CANCER RECEIVING TAR-200 IN COMBINATION WITH CETRELIMAB, TAR-200, OR CETRELIMAB ALONE

LBA02-03 FIRST RESULTS FROM SunRISE-1 IN PATIENTS WITH BCG UNRESPONSIVE HIGH-RISK NON–MUSCLE-INVASIVE BLADDER CANCER RECEIVING TAR-200 IN COMBINATION WITH CETRELIMAB, TAR-200, OR CETRELIMAB ALONE

MP18-09 LIPOSOMAL BUPIVACAINE PLUS BUPIVACAINE VS. BUPIVACAINE ALONE IN PEDIATRIC PATIENTS UNDERGOING UROLOGIC SURGERY: PRELIMINARY REPORT FROM THE BABY ORIOLES TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP18-09 LIPOSOMAL BUPIVACAINE PLUS BUPIVACAINE VS. BUPIVACAINE ALONE IN PEDIATRIC PATIENTS UNDERGOING UROLOGIC SURGERY: PRELIMINARY REPORT FROM THE BABY ORIOLES TRIAL Andrew Gabrielson, Tamir Sholklapper, Chad Crigger, Logan Galansky, Kelly Harris, Hiten PATEL, Nora Haney, Ming-Hsien Wang, Charlotte Wu, John Gearhart, and Heather Di Carlo Andrew GabrielsonAndrew Gabrielson More articles by this author , Tamir SholklapperTamir Sholklapper More articles by this author , Chad CriggerChad Crigger More articles by this author , Logan GalanskyLogan Galansky More articles by this author , Kelly HarrisKelly Harris More articles by this author , Hiten PATELHiten PATEL More articles by this author , Nora HaneyNora Haney More articles by this author , Ming-Hsien WangMing-Hsien Wang More articles by this author , Charlotte WuCharlotte Wu More articles by this author , John GearhartJohn Gearhart More articles by this author , and Heather Di CarloHeather Di Carlo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003238.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Long-acting liposomal bupivacaine (Exparel) was approved for children >6 years old however it has not been evaluated in children undergoing urologic surgery. We report preliminary safety and efficacy data of Exparel plus bupivacaine vs. bupivacaine alone for incisional infiltration or penile block in pediatric patients undergoing ambulatory urologic surgery as part of a randomized trial. METHODS: The study is an IRB-approved prospective, single-blinded trial randomizing patients 6-18 years old 1:1 to receive Exparel plus 0.25% bupivacaine (experimental) vs. 0.25% bupivacaine alone (control) during ambulatory urology procedures (NCT04826484). Patients received Tylenol and Ibuprofen prescriptions and a rescue prescription of 3-5 doses 0.1 mg/kg Oxycodone. Efficacy endpoints include percent requiring no opioids within 48hr and 10-14d, parents’ postoperative pain measure (PPPM) scores at 48hr and 10-14d, and oral morphine equivalents (OMEQ) per kg given through 10-14d. RESULTS: A total of 52 patients (29 control, 23 experimental) have been enrolled. Demographic, procedural, efficacy, and safety data are summarized in Table 1. There was no difference in percentage of patients requiring no post-operative opioids through 48hr (57% vs 55%, p=0.92). There was no difference in mean FLACC score in PACU (0.9 vs 1.2, p=0.64), PPPM score at 48hr (2.5 vs. 3.5, p=0.09) or PPPM score at 10-14d (0.55 vs. 0.6, p=0.67). The experimental arm had significantly reduced OMEQ/kg at 10-14d (0.06 vs. 0.2, p=0.02). However, OMEQ/kg utilization was low and limited to the 48hr post-op period in both arms. There were no intraoperative complications and similar use of perioperative Ketorlac between arms. Roughly 10% of patients in both arms had an unplanned phone call or message to the office (all related to swelling). No patients had unplanned presentation to the emergency department. CONCLUSIONS: This prospective, single-blinded randomized trial is the first to evaluate Exparel in pediatric patients undergoing urologic surgery. We demonstrate that albeit safe, the addition of Exparel to 0.25% bupivacaine did not improve validated pain scores or opioid-free rate at 48 hours. Formal assessment of efficacy and safety pending trial accrual. Source of Funding: Internally funded © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e226 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Gabrielson More articles by this author Tamir Sholklapper More articles by this author Chad Crigger More articles by this author Logan Galansky More articles by this author Kelly Harris More articles by this author Hiten PATEL More articles by this author Nora Haney More articles by this author Ming-Hsien Wang More articles by this author Charlotte Wu More articles by this author John Gearhart More articles by this author Heather Di Carlo More articles by this author Expand All Advertisement PDF downloadLoading ...

Feasibility and usability of a new home-based immersive virtual reality headset-based dexterity training in multiple sclerosis.

Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living and quality of life. The aim of this study was to evaluate the feasibility, usability and patient engagement/satisfaction of a home-based immersive virtual reality (VR) headset-based dexterity training in persons with multiple sclerosis (pwMS). In addition, preliminary efficacy data on the impact of this new training on manual dexterity were collected. Single arm prospective study. After a waiting period of two weeks, pwMS performed a specifically developed home-based VR headset-based dexterity training using the Oculus quest 2 for two weeks with five training sessions/week, each session for approximately 20 minutes. Primary endpoints were feasibility (measured by the adherence rate), usability (System Usability Scale, SUS) and patient engagement/satisfaction (Custom User Engagement Questionnaire, CUEQ). Secondary exploratory efficacy endpoints, measured before and after the waiting period as well as after the training intervention, were the Nine-hole-Peg-Test (9HPT), Coin rotation task (CRT), Handheld JAMAR dynamometer, Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and the Multiple Sclerosis Impact Scale 29 (MSIS 29). Eleven pwMS (mean age 49 ± 10.87 SD, mean EDSS 4.28 ± 1.48 SD) participated in the study. Feasibility (adherence rate: 81.8%), usability (median SUS score 94 (IQR=78-96)) and patient engagement/satisfaction (median 8 on scale of 1-10) of the VR training was very high. In addition, the CRT for the dominant hand improved significantly after training (p=0.03). The good results on feasibility, usability, and patient engagement/satisfaction qualify this home-based immersive VR headset-based dexterity training approach for the use in home-based neurorehabilitation in pwMS. Improved fine motor skills for the dominant hand suggest preliminary efficacy, but this needs to be proven in a future randomized-controlled trials.

CBT + Exercise vs Treatment as Usual in Treating Anxiety and Depression in University Students: A Pilot Study

ABSTRACT The current pilot study tested the feasibility and preliminary efficacy of a combined group cognitive behavioral therapy and exercise intervention (CBT+E), as compared to treatment as usual (TAU) for managing anxiety and mood symptoms in university students. Participants were 16 undergraduate students with at least mild anxiety, depression, or stress symptoms. Participants were randomly assigned to group CBT+E or TAU. CBT+E ran for seven weeks with group sessions held twice weekly. The first weekly session consisted of group CBT followed by 30 minutes of running and the second weekly session consisted of only group running. Findings suggest that the group CBT+E intervention is feasible in terms of retention and participation, but that recruitment strategies need to be improved. Suggestions to improve recruitment in future research are provided. Preliminary efficacy data show positive trends suggesting further pursuit of this type of intervention is important.