Atara Biotherapeutics (United States)

INTEGUMENT-PED/NCT04845620, a 4-week, phase 3 trial, demonstrated efficacy and safety of roflumilastcream 0.05% in children aged 2-5 years with mild-to-moderate atopic dermatitis (AD). A phase 3 open-label extensiontrial(INTEGUMENT-OLE [NCT04804605]) investigated long-term outcomes continuing roflumilast cream for ≤ 56 weeks. Caregivers of eligible patients from INTEGUMENT-PED applied roflumilast cream 0.05% once-daily in INTEGUMENT-OLE. Patients achieving Validated Investigator Global Assessment for AD (vIGA-AD) clear (0) at/afterweek4 of INTEGUMENT-OLE switched to twice-weekly (BIW) application. Evaluation of safety (adverse events [AEs] and application-site tolerability) was the primary objective. Efficacy endpoints assessed from INTEGUMENT-PED baseline included vIGA-AD success (clear/almost clear [0/1] plus ≥ 2-point improvement), vIGA-AD 0/1, ≥ 75% improvement in Eczema Area and Severity Index, and Worst Itch-Numeric Rating Scale success (≥ 4-point improvement in patients with baseline score ≥ 4). Duration of vIGA-AD 0/1 and sign/symptom control ("disease control") with BIW application was determined. Among 562 patients, 14 (2.5%) had treatment-related AEs reported. Roflumilast was well tolerated; application-site pain AEs were reported for four (0.7%) patients. At treatment-week 56, AD signs/symptoms continued to improve (63.1% of patients achieved vIGA-AD 0/1). Of 170 (30.2%) patients who switched to BIW application, the median Kaplan-Meier duration of "disease control" was 238 days. Roflumilast cream 0.05% demonstrated a favorable long-term safety profile and durable efficacy for up to 56 weeks of treatment in children aged 2-5 years with AD, and "disease control" was maintained with BIW application. These results are consistent with previous studies, including patients aged ≥ 6 years from INTEGUMENT-OLE. Clinicaltrials.gov identifier: NCT04845620.

IntroductionTORL-1-23 is a first-in-class ADC targeting the oncofetal protein CLDN6, with expression limited to early stages of development and aberrant expression in several cancers, including ovarian, endometrial, and testicular cancers.MethodsPart 1 (escalation) and part 2 (expansion) will enroll subjects with advanced solid tumors. TORL-1-23 is administered as a 30-minute IV infusion Q3W. Study objectives include evaluation of safety, tolerability, DLTs, RP2D, and antitumor activity. Part 1: subjects received escalating doses of TORL-1-23 across 10 dose levels (0.2 to 4.0 mg/kg). Part 2: subjects with CLDN6-expressing cancers will be evaluated to confirm the RP2D(s) in ovarian cancer, NSCLC, and other CLDN6-expressing cancers using a CLDN6 IHC companion diagnostic.ResultsAs of 31-Jan-2024, Part 1 enrolled 45 subjects with ovarian (n=33), testicular (n=5), and endometrial (n=7) cancers. Median prior lines of systemic therapy were 4 (1-9). Treatment-related adverse events (TRAE) occurred in 86% of subjects. G1/2 TRAEs (>20%) included fatigue (41%), peripheral neuropathy (39%), alopecia (39%), nausea (37%), anemia (24%), WBC count decrease (24%), and arthralgia (22%). The most common (≥10%) G3+ TRAE was neutropenia (20%). Ocular toxicity and ILD were not observed. The ORR across all dose levels was 29% (12/41, all PRs: 10 ovarian, 1 testicular, 1 endometrial), 75% (3/4) at 2.4 mg/kg, and 40% (4/10) at 3.0 mg/kg.Conclusion/ImplicationsTORL-1-23 is well tolerated with promising preliminary antitumor activity in heavily-pretreated patients with CLDN6-expressing ovarian, endometrial, and testicular cancers. Dose expansion is ongoing to optimize the dose for subsequent development.Clinical trial information: NCT05103683. Sponsor: TORL Biotherapeutics.

Aims With recent European Union marketing authorization, tabelecleucel is the first off-the-shelf, allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy approved for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD). In the absence of a control arm, real-world evidence can provide a comparative benchmark for single-arm studies in ultra-rare populations. This study assessed the treatment effect of tabelecleucel in the single-arm phase 3 ALLELE study (NCT03394365) versus a treatment group from a multinational, multicenter retrospective chart review study (RS002) of patients with EBV+ PTLD. Methods In ALLELE, patients had disease relapsed/refractory to rituximab ± chemotherapy and received tabelecleucel 2x106 cells/kg on days 1, 8, and 15 in 35-day cycles. Patients in RS002 had disease relapsed/refractory to rituximab ± chemotherapy and received next line of systemic therapy between January 2000 and December 2018. Propensity score-based standardized mortality/morbidity ratio weighting was used to achieve balance between treatment and comparator arms. Kaplan-Meier estimators and Cox regression models were used to compare overall survival (OS) in the re-weighted sample. Results 30 patients (n = 14 hematopoietic cell transplant [HCT], n = 16 solid organ transplant [SOT]) from ALLELE (data cutoff: November 2021) and 84 patients (n = 36 HCT, n = 48 SOT) from RS002 (data lock: January 2021) were included. Median time from diagnosis to first tabelecleucel dose (ALLELE) or start date of next line of systemic therapy (RS002) was 3.6 months. Tabelecleucel was associated with a substantial OS benefit compared with current treatment, with an unadjusted HR of 0.47 (95% confidence interval [CI] 0.25–0.88) and adjusted HR of 0.37 (95% CI 0.20–0.71) when using the start date of the next line of therapy as the index date. Sensitivity analyses yielded consistent results. Conclusions In this study of real-world data, tabelecleucel was associated with an OS benefit among patients with R/R EBV+ PTLD for whom there is high unmet need.

IntroductionSeborrheic dermatitis (SD) is a common, chronic inflammatory skin condition associated with significant impact on quality of life, yet its etiology and pathophysiology are not well understood. With significant impact on patients’ quality of life, understanding the diagnostic pathway from the perspectives of patient and healthcare providers (HCPs) is crucial.MethodsAn online survey was developed and administered in conjunction with the Harris Poll to gain insight into patient and HCP perspectives about SD diagnosis and management from December 2021 to January 2022.ResultsMost patients were unaware of SD before their diagnosis (71%) and experienced difficulty finding information online (56%). Patients delayed seeking medical attention for SD by an average of 3.6 years, with most patients feeling their symptoms did not require medical attention (63%), a perception that HCPs correctly anticipated. Additionally, most patients (58%) reported embarrassment discussing their SD symptoms with HCPs, a factor HCPs underestimated. HCPs also underestimated the percentage of patients self-reporting moderate-severity SD. Patients preferred dermatology HCPs for SD treatment (79%), and reported visiting an average of 2.3 different HCPs, with 75% of patients seeing more than one provider.ConclusionThese insights highlight the complexities in the diagnostic and management pathways of SD and underscore the need for a more nuanced understanding and approach in addressing the condition.Infographic available for this article.InfographicSupplementary InformationThe online version contains supplementary material available at 10.1007/s12325-024-02986-8.