clinicaltrials.gov Identifier: NCT01693562.

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Association for Cancer Research. D. Campbell has nothing to disclose. A. Patnaik has served in a consulting or advisory role for Exelixis, Janssen, and Jounce Therapeutics; has received honoraria from Clovis Oncology, Merck, Prime Inc, and Roche; and has received research funding from Clovis Oncology, Bristol-Myers Squibb, and GlaxoSmithKline. J. Shapiro has served in a consulting or advisory role for Amgen, Astellas, Ipsen, Merck, and Roche and received financial support for travel from Amgen and Merck. B. Sautois has served a consulting or advisory role for Clovis Oncology, Astellas, Janssen, and Sanofi and received financial support for travel and/or accommodation from Janssen. N.J. Vogelzang has served in a consulting or advisory role for Clovis Oncology,

PURPOSE To assess the safety/tolerability and antitumor activity of enfortumab vedotin (EV), a novel investigational antibody-drug conjugate that delivers the microtubule-disrupting agent, monomethyl auristatin E, to cells that express Nectin-4. METHODS EV-101 is a phase I dose escalation/expansion study that enrolled patients with Nectin-4–expressing solid tumors (eg, metastatic urothelial carcinoma [mUC]) who progressed on ≥ 1 prior chemotherapy regimen and/or programmed death-1 receptor/programmed death ligand-1 [PD-(L)1] inhibitor, including a cohort of patients with mUC who received prior anti–PD-(L)1 therapy. Patients received escalating doses of EV up to 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. Primary objectives were evaluation of safety/tolerability and pharmacokinetics; antitumor activity was a secondary objective. RESULTS Enrolled patients with mUC (n = 155) were heavily pretreated, with 96% having prior platinum-based chemotherapy and 29% receiving ≥ 3 lines of prior treatment. Maximum tolerated dose of EV was not established; however, the recommended phase II dose was identified as 1.25 mg/kg. Rash, peripheral neuropathy, fatigue, alopecia, and nausea were the most common treatment-related adverse events (TRAEs); the most common TRAEs were grade 1-2 in severity. Among the 112 patients with mUC treated with single-agent EV 1.25 mg/kg, the investigator-assessed confirmed objective response rate (ORR) was 43%, and duration of response was 7.4 months. Median overall survival (OS) was 12.3 months, and the OS rate at 1 year was 51.8%. Similar ORR and estimated median OS were observed in patients ≥ 75 years of age with and without prior anti–PD-(L)1 treatment, liver metastases, or upper-tract disease. CONCLUSION Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging. A pivotal phase II and a confirmatory phase III study are ongoing.

Ab initio theoretical studies of potential energy surfaces in the photodissociation of the vinyl radical. I. à state dissociation Photodissociative spectroscopy of the hydroxymethyl radical (CH 2 OH ) in the 3s and 3p x states H-atom channels in the photodissociation of jet-cooled ethyl radical (C 2 H 5 ) via the à 2 AЈ(3s) state are studied near 245 nm by using the high-n Rydberg-atom time-of-flight technique. Bimodal product translational energy release and energy-dependent angular distribution suggest two dissociation pathways. A slow (͗ f T ͘ϳ0.35) and isotropic channel corresponds to unimolecular dissociation of the radical, presumably after internal conversion. A previously unobserved fast (͗ f T ͘ϳ0.78) and anisotropic (␤ϭ0.5Ϯ0.1) channel is consistent with direct H-atom scission via a nonclassical H-bridged transition state from the 3s state to yield HϩC 2 H 4 (X 1 A g ). The fast/slow branching ratio is ϳ0.2. Site-selective loss of the ␤ hydrogen atom is confirmed by using the partially-deuterated CH 3 CD 2 radical.

Recently, MnBi2Te4 has been discovered as the first intrinsic antiferromagnetic topological insulator (AFM TI), and will become a promising material to discover exotic topological quantum phenomena. In this work, we have realized the successful synthesis of high-quality MnBi2Te4 single crystals by solid-state reactions. The as-grown MnBi2Te4 single crystal exhibits a van der Waals layered structure, which is composed of septuple Te-Bi-Te-Mn-Te-Bi-Te sequences as determined by powder X-ray diffraction (PXRD) and high-resolution high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM). The magnetic order below 25 K as a consequence of A-type antiferromagnetic interaction between Mn layers in the MnBi2Te4 crystal suggests the unique interplay between antiferromagnetism and topological quantum states. The transport measurements of MnBi2Te4 single crystals further confirm its magnetic transition. Moreover, the unstable surface of MnBi2Te4, which is found to be easily oxidized in air, deserves attention for onging research on few-layer samples. This study on the first AFM TI of MnBi2Te4 will guide the future research on other potential candidates in the MBixTey family (M = Ni, V, Ti, etc.).

The H + NCO(X211) channel in the 193.3-nm photodissociation of HNCO has been examined by using high-n Rydberg hydrogen atom time-of-flight (HRTOF) spectroscopy, and the center-of-mass (cm) translational energy distribution has been obtained. The cm translational energy distribution peaks near the maximum available energy and shows considerable structure corresponding to NCO vibrational excitation. This is attributed to geometric changes in going from HNCO to the electronically excited potential surface then to products. Specifically, a strongly bent N-C-0 angle in excited HNCO accounts for the long NCO bending progression that is observed. A strongly anisotropic product angular distribution was observed, in agreement with an 'A" excited state and rapid dissociation via a repulsive surface. Do(H-NCO) is found to be 110.1 f 0.5 kcal mol-', in agreement with recent experimental and theoretical values.

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