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Background: This study investigated the safety and efficacy of an anti–CTLA‐4 monoclonal antibody (CS1002) as monotherapy and in combination with an anti–PD‐1 monoclonal antibody (CS1003) in patients with advanced/metastatic solid tumors. Methods: The phase 1 study involved phase 1a monotherapy dose‐escalation (part 1) and phase 1b combination therapy dose escalation (part 2) and expansion (part 3). Various dosing schedules of CS1002 (0.3, 1, or 3 mg/kg every 3 weeks, or 3 mg/kg every 9 weeks) were evaluated with 200 mg CS1003 every 3 weeks in part 3. Results: Parts 1, 2, and 3 included a total of 13, 18, and 61 patients, respectively. No dose‐limiting toxicities or maximum tolerated doses were observed. Treatment‐related adverse events (TRAEs) were reported in 30.8%, 83.3%, and 75.0% of patients in parts 1, 2, and 3, respectively. Grade ≥3 TRAEs were experienced by 15.4%, 50.0%, and 18.3% of patients in each part. Of 61 patients evaluable for efficacy, 23 (37.7%) achieved objective responses in multiple tumor types. Higher objective response rates were observed with conventional and high‐dose CS1002 regimens (1 mg/kg every 3 weeks or 3 mg/kg every 9 weeks) compared to low‐dose CS1002 (0.3 mg/kg every 3 weeks) in microsatellite instability‐high/mismatch repair‐deficient tumors, melanoma, and hepatocellular carcinoma (50.0% vs. 58.8%, 14.3% vs. 42.9%, and 0% vs. 16.7%). Conclusion: CS1002, as monotherapy, and in combination with CS1003, had a manageable safety profile across a broad dosing range. Promising antitumor activities were observed in patients with immune oncology (IO)‐naive and IO‐refractory tumors across CS1002 dose levels when combined with CS1003, supporting further evaluation of this treatment combination for solid tumors. Plain Language Summary: CS1002 is a human immunoglobulin (Ig) G1 monoclonal antibody that blocks the interaction of CTLA‐4 with its ligands and increases T‐cell activation/proliferation. CS1003, now named nofazinlimab, is a humanized, recombinant IgG4 monoclonal antibody that blocks the interaction between human PD‐1 and its ligands.In this original article, we determined the safety profile of CS1002 as monotherapy and in combination with CS1003. Furthermore, we explored the antitumor activity of the combination in anti–programmed cell death protein (ligand)‐1 (PD‐[L]1)‐naive microsatellite instability‐high/mismatch repair‐deficient (MSI‐H/dMMR) pan tumors, and anti–PD‐(L)1‐refractory melanoma and hepatocellular carcinoma (HCC).CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising antitumor activities across CS1002 dose levels when combined with CS1003. This supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors. This was a phase 1a/1b, dose‐escalation and dose‐expansion study evaluating the safety and efficacy of an anti–CTLA‐4 monoclonal antibody (CS1002) as monotherapy and in combination with an anti–PD‐1 monoclonal antibody (CS1003/nofazinlimab), in patients with advanced/metastatic solid tumors. Promising antitumor activities were observed in heavily pretreated patients with immune oncology (IO)‐naive and IO‐refractory tumors across CS1002 dose levels when combined with CS1003, which supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors. [ABSTRACT FROM AUTHOR]

The prediction of crystal structures is of great significance in the community of energetic materials since the crystal packing pattern is closely linked to the energetic and safety features. Here, we developed a tailor-made polarizable force field (TMPFF) calibrated by the benchmarks obtained from ab initio methods and applied it with the USPEX evolutionary algorithm to predict crystal structures from energetic molecular structures. The results showed that the prediction results of three polymorphs of hexaazaisowurtzitane (CL-20) all agree well with experimental measurements, for both lattice parameters and packing patterns. This work provides a new solution to predict polymorphs of CHON-based energetic molecules with high accuracy and good efficiency and shall accelerate the cognition process of new energetic crystals by theoretical approaches prior to experimental synthesis. [ABSTRACT FROM AUTHOR]

Governments in many countries have offered various incentives to promote the diffusion of electric vehicles (EVs). This study examines the effectiveness of various policy measures that underlie the rapid development of the EV market in China, by far the world's largest such market. The analysis is based on detailed data on EV sales, local and central government incentive programs, and charging stations in 150 cities from 2015 to 2018. The empirical framework addresses the potential endogeneity of key variables, such as local policies and charging infrastructure, by using a city‐border‐regression design and instrumental variable approach. We find that consumer subsidies for vehicle purchases accounted for more than half of EV sales in China. Nevertheless, investments in charging infrastructure were much more cost‐effective than consumer subsidies. An inexpensive policy that merely provided EVs with a distinctive, green license plate was strikingly effective. These findings demonstrate the varying efficacy of different policy instruments and highlight the critical role of the government in promoting clean technologies. [ABSTRACT FROM AUTHOR]