ABSTRACTMDX2001 is a tetraspecific T-cell engager-expander antibody engineered to recognize four distinct antigens: cellular mesenchymal-epithelial transition factor (c-MET) and trophoblast antigen 2 (TROP2) to direct T cells to tumor cells, CD3 to activate T cells, and CD28 to enhance T-cell survival and proliferation. MDX2001 has demonstrated potent antitumor activity in nonclinical studies over a wide range of tumor types. Here, we present the protocol design for study MDX-2001–101, a multicenter, open-label, phase I/IIa clinical trial designed to evaluate the safety, tolerability, and antitumor effects of MDX2001 in patients with advanced solid tumors. The study comprises a phase Ia dose escalation guided by a Bayesian optimal interval design with a targeted maximum tolerated dose toxicity rate of 30%, a phase Ib dose expansion, and a phase IIa indication expansion.

ABSTRACTThe role of perioperative immunotherapy as a chemotherapy-free option for patients with resectable mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colon cancer is evolving, with early-phase neoadjuvant studies reporting favorable long-term outcomes. AZUR-2 is an ongoing global, Phase III, open-label, randomized study evaluating the efficacy of perioperative dostarlimab monotherapy compared with standard of care (SoC) (adjuvant chemotherapy or surveillance) in adult patients with previously untreated, pathologically confirmed, radiologically evaluable T4N0 or Stage III resectable dMMR/MSIH colon adenocarcinoma. Patients will be randomized 2:1 to receive neoadjuvant dostarlimab 500 mg every 3 weeks (4 cycles), followed by surgery, then adjuvant dostarlimab 1000 mg every 6 weeks (6 cycles), or to receive immediate surgery followed by SoC. The primary endpoint is event-free survival assessed by blinded independent central review. The key secondary endpoint is overall survival; additional secondary endpoints include pathological response assessed by residual viable tumor determined by local assessment, safety, and tolerability.Clinical trial registration: NCT05855200 (www.clinicaltrials.gov).

ABSTRACTPatients with prostate cancer treated with radiotherapy (RT) or radical prostatectomy (RP) as primary therapy may develop biochemical recurrence (BCR), which requires effective treatment to delay disease progression. The ARASTEP study (NCT05794906) aims to determine whether the addition of darolutamide to androgen-deprivation therapy (ADT) improves radiologic progression-free survival (rPFS) using prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared with placebo plus ADT in patients with high-risk BCR.Approximately 970 patients from 243 sites globally will receive either darolutamide 600 mg or placebo twice daily, both with ADT, for 24 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Eligible patients will have been treated by primary RT or RP ± adjuvant RT (ART) or salvage RT (SRT), and present with high-risk BCR (prostate-specific antigen [PSA] doubling time <12 months and PSA ≥0.2 ng/mL after RP [± ART/SRT] or PSA ≥2 ng/mL above nadir after primary RT only), ≥1 PSMA PET/CT-positive lesion (negative on conventional imaging), serum testosterone >150 ng/dL, and Eastern Cooperative Oncology Group performance status 0/1. The primary endpoint is rPFS using PSMA PET/CT, with secondary endpoints including metastasis-free survival, time to castration-resistant prostate cancer, overall survival, quality of life, and safety.CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05794906.

ABSTRACTThe integration of genomic tests such as the Oncotype DX Breast Recurrence Score® test, into routine clinical practice represents a significant advance in personalized breast cancer care. By supporting more tailored therapeutic decisions, these diagnostics can improve patient outcomes, while reducing risks of undertreatment, overtreatment, and associated side effects. Cost-effectiveness has already been demonstrated in numerous publications. However, for widespread adoption across Europe, four principal challenges must be overcome: regulation, technology assessment, reimbursement, and gaps in real-world evidence. Since May 2022, the European Union In Vitro Diagnostics Regulation (IVDR) has updated requirements for demonstrating clinical utility and analytical and scientific validity, creating new barriers for manufacturers regarding primary evidence generation. Variability in health technology assessment (HTA) frameworks and reimbursement mechanisms across countries further complicates adoption. Demonstrating real-world benefits of these technologies requires robust, representative data collections, yet current clinical trial evidence often underrepresents certain patient populations, raising equity concerns. Whilst the IVDR will help standardize regulatory requirements, challenges remain in harmonizing evidence standards for HTA and reimbursement. This review explores these barriers using the Oncotype DX® test as an exemplar. Evidence was drawn from targeted literature searches and reviews of regulatory, reimbursement, and gray literature relevant to European healthcare systems.

ABSTRACTAimBecause no conclusive data demonstrate superiority among NK1 receptor antagonists (RA), existing antiemetic guidelines regard them as interchangeable. This individual patient data (IPD) meta-analysis compared the efficacy of NEPA (netupitant/fosnetupitant) and aprepitant/fosaprepitant-based regimens in preventing chemotherapy-induced nausea and vomiting (CINV).Materials & MethodsHead-to-head comparative studies published between 2003 and 2022 that evaluated antiemetic prophylaxis of aprepitant or fosaprepitant versus oral or intravenous (IV) NEPA in patients with various cancers receiving highly (HEC) or moderately emetogenic chemotherapy (MEC) were identified through a literature search. We combined individual patient data to assess complete response (no emesis/no rescue medication) and no significant nausea using a two-stage approach.ResultsA total of six studies involving 2,767 patients were included evaluating NEPA plus dexamethasone versus aprepitant/fosaprepitant plus any 5-HT3RA plus dexamethasone for patients with cancer receiving HEC/MEC. Complete response and no significant nausea rates were similar during the acute (0–24 h) phase but NEPA showed significantly higher rates than aprepitant during the delayed ( > 24–120 h) and overall (0–120 h) phases and on Days 3–5 following chemotherapy.ConclusionImproved CINV prevention was observed with NEPA-based regimens, particularly during Days 3–5, highlighting its potential for managing prolonged nausea and vomiting associated with emerging anticancer targeted therapies.

ABSTRACTBackgroundB-cell maturation antigen (BCMA)-targeted therapies were approved for triple-class exposed relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy.MethodsThis claims-based retrospective analysis examined clinical and economic burden among United States patients who met eligibility for BCMA-targeted therapies and started a new therapy between 1 January 2016 and 30 September 2022.ResultsOf 228 eligible patients (median age: 64, 52.6% male, 68.7% White), clinical burden was characterized by prevalent MM-related conditions and complications, and high treatment failure rate (44.7% in 6 months). Hospitalization rate increased from 48.3% to 71.1%, while healthcare costs per-member-per-month increased from $35,964 during 12-month baseline to $41,358 during follow-up (median: 11.8 months).ConclusionsPatients with heavily pre-treated RRMM endure high disease burden and could benefit from novel therapies.

ABSTRACTBackgroundThis post-marketing surveillance evaluated the safety and effectiveness of tirabrutinib in patients with relapsed/refractory primary central nervous system lymphoma (r/r PCNSL) in a real-world setting in Japan.MethodsAll patients with r/r PCNSL who started treatment with tirabrutinib between May 20 and 31 October 2020, were registered. Adverse drug reactions (ADRs) and effectiveness were assessed over 52-weeks from the start of tirabrutinib treatment.ResultsOf the 189 patients assessed for safety, 52.4% were male, the median age was 70.0 years (range 30–88), and 49.2% of patients had a Karnofsky performance status score of ≤60. ADRs of any grade and grade ≥3 were observed in 55.6% and 24.3% of patients, respectively. The most common ADRs were rash (11.6%), neutrophil (10.1%) and platelet (5.3%) count decreased. Most of the ADRs corresponding to infections, clinically significant skin disorders, myelosuppression, hypersensitivity, interstitial lung diseases, hepatic function disorders, and hemorrhages resolved or were in the process of resolving. Among the 121 patients assessed for effectiveness, the overall response rate evaluated by the treating physicians was 61.2%, and the 365-day survival rate was 69.8%.ConclusionThis surveillance confirmed the tolerability and effectiveness of tirabrutinib in patients with r/r PCNSL in the real-world setting.Clinical trial registrationJapan Registry of Clinical Trials: jRCT2011210002.