Protein tyrosine kinase 7 (PTK7) overexpression in lung cancer is associated with tumor progression. Cofetuzumab pelidotin (Cofe-P) is an antibody-drug conjugate comprising an anti-PTK7 antibody conjugated to a microtubule inhibitor. Herein, we report the results of a phase 1b study evaluating Cofe-P safety, efficacy, and pharmacokinetics in patients with recurrent non-small cell lung cancer (NSCLC). This signal-seeking phase 1b, open-label, multicenter, single-arm study enrolled patients with PTK7-expressing recurrent NSCLC. Cofe-P was administered at 2.8 mg/kg intravenously once every 3 weeks. The primary endpoint was objective response rate (ORR) and secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Overall, 65 patients received Cofe-P; 51 had PTK7 expression of ≥90 % tumor cells with ≥2+ staining intensity by immunohistochemistry. All patients reported adverse events (AEs), most commonly alopecia (52 %) and decreased neutrophil count (43 %); 69 % had grade ≥3 AEs, including grade ≥3 neutropenia in 25 %. Treatment-related AEs were reported in 94 % of patients; none were fatal. Overall, ORR was 18 %; in patients with PTK7 expression of ≥90 % tumor cells with ≥2+ staining and non-squamous epidermal growth factor receptor (EGFR) wild type or mutant, or squamous NSCLC, ORR was 21 %, 15 %, and 13 %, respectively. Overall, median DOR was 7.2 months, median PFS was 5.5 months, and median OS was 12.6 months; longest DOR (median 9.0 months), PFS (median 6.8 months), and OS (median 12.6 months) were in patients with non-squamous EGFR-mutant NSCLC. Cofe-P demonstrated a manageable safety profile and preliminary efficacy across NSCLC histologies and EGFR mutation status. These data support PTK7 as a valid therapeutic target for NSCLC.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered for patients with high-risk B-cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long-term follow-up data of patients who underwent allo-HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo-HSCT because of high-risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty-five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow-up duration was 18.6 months. The probability of 3-year progression-free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1-year non-relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft-versus-host disease (GVHD) were factors associated with inferior OS. The probability of 3-year OS in patients with diffuse large B-cell lymphoma who underwent allo-HSCT and allo-HSCT after ASCT was 40.2% and 25.2%, respectively. Allo-HSCT could be a salvage therapeutic option for relapsed or refractory B-cell lymphoma. Complete remission at the time of allo-HSCT and the presence of GVHD are independent variables for overall survival. From our data, allo-HSCT could be a salvage therapeutic option for relapsed or refractory B-cell lymphoma. Complete remission at the time of allo-HSCT and presence of GVHD are independent variables for overall survival.image

Introduction: Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) testing is emerging as a tool to refine relapse risk and guide surveillance after curative-intent therapy for non-small cell lung cancer (NSCLC). Tissue-free (plasma-only) MRD assays may improve feasibility where tumor tissue is limited. Prospective and trial-embedded studies have established that ctDNA MRD detected after curative-intent therapy is prognostic for recurrence in NSCLC, but how tissue-free MRD testing is deployed in routine care in Asia-Pacific and the Middle East (AMEA) has not been described. We characterized ordering patterns and first-test positivity in an AMEA cohort. In this descriptive cohort (159 NSCLC patients; 257 samples), 40.9% of patients underwent more than one MRD test, with a median interval of 4.9 months between the first two tests; first-test MRD positivity was 15.7% (25/159; 95% CI 10.9–22.2) with rates of 0% (0/9; 95% CI 0.0–29.9), 8.8% (5/57; 95% CI 3.8–18.9), 21.5% (17/79; 95% CI 13.9–31.8) and 21.4% (3/14; 95% CI 7.6–47.6), respectively, across stages I, II, III, and oligometastatic stage IV disease. No hypothesis testing was performed, and the stage I and oligometastatic stage IV subgroups are small, so the confidence intervals overlap widely and apparent between-stage differences should not be interpreted as a stage effect. Case Presentation: Six illustrative cases involving patients with stage II–IVB describe the use of MRD testing in routine clinical care. The cases were selected purposively, not consecutively, to span the contexts in which the results were interpreted: a positive result shortly before radiographic nodal recurrence (Case 1); a positive result during long-term adjuvant osimertinib preceding isolated mediastinal relapse (Case 2); a transient positive result with subsequent clearance and radiographic regression (Case 3); a positive result that prompted PET-CT revealing occult metastatic disease (Case 4); serially negative results concordant with sustained radiographic remission (Case 5); and a positive result that prompted comprehensive genomic profiling identifying an actionable KRAS G12C alteration (Case 6). Conclusions: Across Asia-Pacific and the Middle East, tissue-free MRD testing in NSCLC was used primarily during surveillance and often serially; first-test positivity was 15.7% (95% CI 10.9–22.2) overall, with wide and mutually overlapping confidence intervals across stages. The cases illustrate that MRD results may prompt diagnostic evaluation when interpreted alongside imaging and other clinical findings, but they are purposively selected, and treatment changes that followed a result are reported as description, not as evidence of benefit. No assay performance characteristic is estimated. These findings are hypothesis-generating; prospective, MRD-directed trials with standardized timepoints, thresholds, confirmatory strategies and pre-specified clinical actions are needed before MRD results can guide treatment.