bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab plus apatinib for advanced renal cell carcinoma patients after first-line tyrosine kinase inhibitor treatment failure: A multicenter phase II trial.
Authors: Jiang Lijuan , Zheng Xia , Wei Wensu , Peng Yulu , Wang Deling , Zhang Zhiling , Guo Shengjie , Han Hui , Cai Xiuyu , Zhou Fangjian , Dong Pei 
Published: July 2024

4539 Background: Previous studies have demonstrated the benefit of combining immunotherapy with antiangiogenic agents in patients with advanced renal cell carcinoma (aRCC). The efficacy of apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (TKI), has been documented in aRCC. In contrast, the efficacy of camrelizumab, a PD-1 inhibitor, has not been reported in RCC, although its efficacy and safety have been established in various cancer types. This study aims to evaluate the efficacy and safety of camrelizumab plus apatinib in aRCC following the failure of first-line TKI therapy. Methods: This multicenter, single-arm, phase II trial enrolled patients with aRCC who had failed first-line TKI treatment. Patients received 200 mg of camrelizumab intravenously every two weeks and 250 mg of apatinib orally once daily until disease progression or unacceptable toxicity occurred, with camrelizumab treatment lasting up to two years. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Between August 2020 and January 2024, 35 patients were enrolled in the study and received treatment. The median age was 57 years (range: 39-81), with 31 (88.6%) being male. A total of 27 (77.1%) patients presented with lung metastases. As of the cut-off date, January 8, 2024, the median follow-up duration was 16.5 months (range: 0-33). Of these patients, 12 (34.3%) achieved a partial response, and 17 (48.6%) maintained stable disease, resulting in an objective response rate of 34.3% (95% confidence interval [CI], 19.1-52.2) and a disease control rate of 82.9% (95% CI, 66.4-93.4). Two out of five patients with progressive disease (PD) benefited from continued treatment with camrelizumab plus apatinib for more than 4 months after the first PD. The median PFS was 10.0 months (95% CI, 6.1-14.9), and the median overall survival was 28.4 months (95% CI, 19.7-not reached). Of all patients, 27 (77.1%) experienced treatment-related adverse events of grade 3 or higher, with the most common being proteinuria (25.7%), hypertension (20.0%), and alanine aminotransferase increased (14.3%) and aspartate aminotransferase increased (14.3%). Conclusions: The combination of camrelizumab and apatinib demonstrates encouraging antitumor activity and a favorable safety profile as a second-line treatment option for patients with aRCC. Clinical trial information: ChiCTR2000034384. [Table: see text]
Updated results from a phase II study of penpulimab plus anlotinib as first-line therapy in metastatic urothelial cancer (mUC).
Authors: Yang Bo , Xiong Qi , Song Qi , Long Yaping , Guo Gang , Li Hongzhao 
Published: July 2024

4573 Background: Cisplatin-based chemotherapy is the standard-of-care systemic treatment for mUC patients with good physical status and organ function, which has shown a response in more than 40% of patients, with mOS approximately 15 months. With the advent of immune checkpoint inhibitors, there are more explorations and options for first-line treatment of locally advanced or mUC. However, here is an ongoing unmet need for improved first-line treatment. Immune checkpoint inhibitors combined with anti-angiogenic therapy have a synergistic effect. Studies have reported that penpulimab combined with anlotinib have good efficacy and safety in multiple solid tumors. This study aimed to evaluate the efficacy and safety of penpulimab plus anlotinib as first-line therapy for mUC (ChiCTR2200056732). Methods: In the single-arm, phase Ⅱ study, eligible patients were aged 18-75 years with mUC who had no prior systemic therapy and ineligible or rejected for cisplatin-based therapy or any platinum-based chemotherapy, measurable lesion (according to RECIST v1.1), and ECOG PS of 0-2. Patients received penpulimab 200 mg intravenously on day 1 and anlotinib 8 mg orally once daily on day 1 to 14 every 3 weeks until progression, intolerable toxicities, or completion of 24 months of treatment. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: From Feb. 2020 to Dec. 2023, 29 patients of mUC were successfully enrolled and received at least once time treatment. Among them, 79.3% (23/29) were males and 20.7% (6/29) were females, with a median age of 64 years (range, 49-74). 10 of 29 (34.48%) patients had a history of smoking. 24.1% (7/29), 72.4% (21/29) and 3.45% (1/29) patients were ECOG PS 0, 1 and 2, respectively. PD-L1 expression was detected in 25 patients, of whom 52.0% (13/25) had TPS < 1, 36.0% (9/25) had TPS≥1%, <50%, and 12.0% (3/25) had TPS≥50%. At data cutoff (January. 1. 2024), a total of 24 patients were evaluated with a median follow-up time of 8.3m (95% CI, 2.8-13.8). The ORR was 62.5% (95% CI, 40.6-81.2) and DCR was 95.8% (95% CI, 78.9-99.9). The median PFS was 12.1 months (95% CI, 3.5-20.7). The median OS was not reached and 12-month OS rate was 100%. Frequent treatment-related adverse events of all grades included creatinine increased (16.7%) and transaminase elevation (10.0%). Grade 4 toxicity of liver dysfunction occurred in two patient (6.9%). No treatment-related death was observed. Conclusions: Penpulimab plus anlotinib demonstrated promising antitumor activity and manageable safety profile with no new safety signal in mUC. Clinical trial information: ChiCTR2200056732.
EX103: A newly designed CD20×CD3 molecule in heavily pre-treated patients with B-cell non-Hodgkin lymphoma from a phase I/II trial.
Authors: Sun Mingyuan , Qi Junyuan , Zhou Keshu , Liu Xingchen , Hu Kai , Chang Chunkang , Wu Dong , Li Zhenling , Gong Ming , ZHANG WENJUN , Yang Daniel Chunxu , LU JIALI 
Published: July 2024

7022 Background: T-cell-engaging bispecific antibody (TCB) had emerged as a promising therapy for blood malignancies, including relapsed/refractory (R/R) B-NHL. However, severe cytokine release syndrome (CRS) remains to be a significant challenge in TCB treatment. To overcome this setback, we re-designed a new CD20xCD3 bispecific antibody (EX103) with a lower affinity to CD3. Clinical data from an ongoing first-in-human phase I/II study demonstrates that EX103 has an encouraging safety and promising single-agent antitumor activity in heavily pretreated R/R B-NHL patients. We present updated safety and efficacy data from the ongoing trial (CTR20212096). Methods: Eligible patients received EX103 with 3 step-up doses followed by target doses in 28-day cycles (iv, QW: cycle 1-2; Q2W thereafter) until disease progression or unacceptable toxicity. At data cut off (Dec 24, 2023), a total of 23 patients were evaluated, including 18 patients in dose-escalation part and 5 patients in dose-expansion part. Results: Among 23 evaluable patients (median age: 51 years [range 42-70]; median prior lines of treatment: 4 [range 2-10]), 13 patients had diffuse large B-cell lymphoma (DLBCL), 4 had FL 1-3a, 2 had FL grade 3B, 1 had marginal zone lymphoma, 1 had mantle cell lymphoma, and 2 had chronic lymphocytic leukemia. Median time since last therapy was 2.5 (range 0.3-39.2) months. No DLT and treatment-related death were observed. CRS was the most common treatment related adverse event. All CRS events were grade (Gr) 1-2 (Gr 1: 78.3%, Gr 2: 13.0%), no Gr 3 or higher events. Most CRS events occurred in the first or second treatment cycle, and all CRS-related clinical symptoms were resolved within 48 hours. No cases of immune effector cell-associated neurotoxicity syndrome or other clinically significant neurologic AEs were observed. For dose ≥ 6 mg cohorts, the overall response rate (ORR) for aggressive B-NHL is 78.6% and the complete response (CR) rate is 50.0% (14 patients). Meanwhile, the ORR for indolent B-NHL is 100%, and CR rate is 25.0% (4 patients). The overall DCR is 89.5%. Currently, treatment is ongoing for 18 patients. The longest duration of response is 14 months. Patients who were refractory to previous therapies achieved impressive responses to EX103 treatment. 3 patients who failed CAR-T therapy achieved either CR or partial response (PR) (2 CR and 1 PR), 2 patients who failed CD19×CD3 bispecific antibody treatment both achieved PR, and 4 patients who failed ASCT achieved either CR or PR (2 CR and 2 PR). Conclusions: EX103 can induce deep and durable responses in heavily pretreated patients with R/R B-NHL, such as those patients who failed CAR-T treatment (3 cases), CD19xCD3 bispecific antibody treatment (2 cases) and ASCT (4 cases). Clinical trial information: CTR20212096.
Neoadjuvant hypofractionated radiotherapy combined with pembrolizumab plus chemotherapy for potentially resectable non-small cell lung cancer: A phase Ib study.
Authors: Ding Naixin , Zhao Lijun , Zhang Shuai , Qiu Ninglei , Song Xue , Kong Cheng , Jiang Ning , Zhao Yang , Huang Jianfeng , Jiang Feng , Jiang Ming , Zhu Zihao , Yin Rong , Ren Binhui , Zhu Xiangzhi , Li Ming 
Published: July 2024

8054 Background: Neoadjuvant PD-1 inhibitor plus chemotherapy in resectable non-small cell lung cancer (NSCLC) has become a standard of care. hypofractioned radiotherapy (HFRT) served as an immunomodulator and enhanced the effect of preoperative immunotherapy. In this phase Ib study, we evaluated the safety and feasibility of neoadjuvant HFRT with pembrolizumab plus chemotherapy in patients with potentially resectable stage III NSCLC. Methods: Patients with potentially resectable stage III NSCLC with EGFR/ALK wild-type were recruited to receive HFRT to the primary tumor followed by two cycles of pembrolizumab (100 mg/body) plus platinum-based doublet chemotherapy (Q3W). HFRT was delivered using 3 daily fractions, with a dose of 24 Gy for peripheral lesions and 12 Gy for central lesions. Central lesion is defined as a 2 cm area around the pulmonary artery and main bronchus. The decision for surgery was made through multidisciplinary team (MDT) discussion within a 4–6-week period after the completion of neoadjuvant treatment. Patients underwent surgery followed by adjuvant pembrolizumab for 2 years. Primary endpoint was safety. Secondary endpoints were efficacy, such as pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: Between April 2021 and November 2023, 17 patients were enrolled with a median age of 66 years (range 54-74) and 15 (88.2%) having squamous cell lung cancer. 12 (70.6%) patients had stage IIIB disease, and 10 (58.8%) had central primary lesion. PD-L1 was ≥1% in 9 patients (52.9%). All patients received HFRT and at least one cycle of immunochemotherapy. No grade 3 or high adverse events were observed during neoadjuvant therapy. Only one patient had grade 1 nephrotoxicity, and another patient had grade 2 pneumonitis. A partial response was achieved in 16 out of 17 patients (94.1%), while one patient had stable disease after neoadjuvant therapy. Following MDT discussion, 11 patients (64.7%) met the surgical standards, while the remaining 6 patients were transitioned to definitive chemoradiotherapy. Among the 11 patients who underwent surgery, 8 (72.7%) achieved R0 resection, and 6 patients (54.5%) attained pCR. Only one patient died from intraoperative bleeding, and the remaining patients were followed up. The median PFS was 21.7 months, median OS were not reached, and the 2-year OS rate was 85.6%. The study was terminated early due to slow recruitment. Conclusions: Neoadjuvant HFRT with immunotherapy for potentially resectable stage III NSCLC is a tolerable treatment with an improved surgical conversion rate and pCR rate. Clinical trial information: ChiCTR2100045361.
The safety and efficacy of induction chemoimmunotherapy in initially unresectable stage III non-small cell lung cancer.
Authors: Tang Min , Zhao Zhe , Zhang Ping , Nie Xin , Wu Xiaonan , Yuan Yue , Liu Lian , Liu Lipin , Jiao Peng , Li Lin 
Published: July 2024

8058 Background: Definitive concurrent chemoradiation followed by consolidation immunotherapy is the standard of care for unresectable stage III non-small cell lung cancer. Several studies demonstrated addition of induction immunotherapy may further improve outcome, and it is necessary to assess the response-adapted strategy based on early tumor retraction to induction therapy. This study evaluated safety and treatment outcomes of induction chemoimmunotherapy followed by surgery or RT in unresectable stage III NSCLC. Methods: Patients with previously untreated, unresectable, pathologically and radiologically confirmed stage III NSCLC, EGFR/ALK-wild-type, with measurable disease were included. Patients received 3 to 4 cycles (Q3W) of chemoimmunotherapy including carboplatin (area under the curve [AUC] 5mg/mL/min), nab-paclitaxel (squamous NSCLC, 260mg/m2) or pemetrexed (non-squamous NSCLC, 500mg/m2), and tislelizumab(200mg). After Multi-Disciplinary Treatment, those operable patients after induction chemoimmunotherapy received radical minimally invasive surgery followed by 14 cycles of tislelizumab. The still unresectable patients received standard thoracic radiotherapy followed by 14 cycles of tislelizumab. Coprimary end points include 24-month progression-free survival (PFS) rate and incidence of grade 3 to 5 pneumonitis. Results: Between May 2020 and November 2023, a total of 59 patients received treatment (54 men [91.5%]; median [range] age, 65 [46-82] years; 34 patients [57.7%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥ 1%); 40 patients [67.8%] were squamous cell NSCLC; 33.9%, 45.8%, and 20.3% patients were stage IIIA, IIIB and IIIC. Sixteen patients received radical minimally invasive surgery (9 pCR), 42 patients received thoracic radiotherapy, and 1 patient had brain metastasis after 2 cycles of induction therapy. The median follow-up period was 20.1 (1.9-44.1) months, and median PFS was not reached, the 24-months PFS rate was 77.6% (95%CI, 59.9%-88.2%). The objective response rate was 93.2% (95%CI, 83.5%-98.1%), and DCR was 98.3% (95%CI, 90.9%-100.0%). Grade 3 pneumonitis occurred in 2 of 59 patients (3.4%). Conclusions: The findings of this study indicate encouraging antitumor activity and manageable safety of induction chemoimmunotherapy, and the response-adapted strategy requires further exploration in locally advanced unresctable non-small cell lung cancer. Clinical trial information: ChiCTR2200064104. [Table: see text]
Comparison of ICI plus chemotherapy or ipilimumab plus nivolumab based therapy for patients with NSCLC with TPS (1-49%): TOPGAN2023-01.
Authors: Tozuka Takehiro , Tanaka Hisashi , Makiguchi Tomonori , Kawashima Yosuke , Oba Tomohiro , Tsugitomi Ryosuke , Koyama Junji , Tambo Yuichi , Ogusu Shinsuke , Saiki Masafumi , Gyotoku Hiroshi , Hasegawa Tsukasa , Miyauchi Eisaku , Sonoda Tomoaki , Saito Ryota , Nakatomi Katsumi , Sakatani Toshio , Kudo Keita , Tsuchiya-Kawano Yuko , Nishio Makoto 
Published: July 2024

8550 Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.
Long-term efficacy and safety of larotrectinib in patients with TRK fusion lung cancer.
Authors: Drilon Alexander E. , Kummar Shivaani , Lin Jessica Jiyeong , Tan Daniel Shao-Weng , Moreno Victor , Leyvraz Serge , Dubashi Biswajit , KP Haresh , Burcoveanu Domnita-Ileana , Neu Natascha , Mussi Chiara E. , Shen Lin 
Published: July 2024

8570 Background: NTRK gene fusions are oncogenic drivers in lung cancer and other cancers. Larotrectinib is the highly selective and central nervous system (CNS)-active TRK inhibitor approved for use in patients with TRK fusion cancer based on a robust and durable overall response rate (ORR) in patients with various tumor types. Here, we report long-term efficacy and safety in a cohort of patients with TRK fusion lung cancer treated with larotrectinib. Methods: Patients with TRK fusion lung cancer treated with larotrectinib in two clinical trials (NCT02122913, NCT02576431) were included. Larotrectinib was administered at 100 mg twice daily. Response was assessed by an independent review committee (IRC) per RECIST v1.1. Results: As of July 20, 2023, 32 patients with a median age of 55.5 years (range 25-81) with TRK fusion lung cancer were enrolled, including 12 patients with CNS metastases at baseline. NTRK gene fusions were identified by next-generation sequencing in all 32 patients. The gene fusions involved NTRK1 (n=24; 75%) and NTRK3 (n=8; 25%). Patients had received a median of two prior lines of systemic therapies; one patient was treatment-naïve. The ORR per IRC was 66% (95% confidence interval [CI] 47-81): four complete responses, 17 partial responses, seven stable disease, two progressive disease, and two not evaluable. Median time to first response was 1.8 months (range 1.5-7.3). Median duration of response (DoR) was 33.9 months (95% CI 9.5-not estimable [NE]); median follow-up was 25.8 months. Median progression-free survival (PFS) was 22.0 months (95% CI 9.9-NE); median follow-up was 27.7 months. Median overall survival (OS) was 39.3 months (95% CI 17.2-NE); median follow-up was 32.9 months. The 48-month rates for DoR, PFS, and OS were 47% (95% CI 19-76), 34% (95% CI 11-56), and 38% (95% CI 13-64), respectively. Duration of treatment ranged from 2 to 75+ months. At the data cutoff, 11 patients had progressed; six patients continued treatment post-progression for ≥4 weeks due to continued clinical benefit. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. Grade 3/4 TRAEs were reported in nine patients. One patient discontinued treatment due to TRAEs (increased alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase). Conclusions: Larotrectinib continued to demonstrate rapid and durable responses, extended survival benefit, and a favorable safety profile in patients with advanced TRK fusion lung cancer. These results support the wider adoption of next-generation sequencing panels that include NTRK gene fusions in patients with lung cancer to identify those who may benefit from targeted treatment. Clinical trial information: NCT02122913 , NCT02576431 .
An open-label, multicenter phase 1 study to characterize safety, tolerability, preliminary antitumor activity, and pharmacokinetics of VIP236 monotherapy in patients with advanced cancer.
Authors: Vandross Andrae L. , Stein Brian N. , Coward Jermaine , Sharma Sunil , Johnson Amy J. , Birkett Joseph , Huang Xin , Frigault Melanie M. , Lerchen Hans-georg , Stelte-Ludwig Beatrix , Navarro Tasheda , Peck Jim , Gross Wyatt , Izumi Raquel , Hamdy Ahmed M. , Rodriguez Rivera Ildefonso 
Published: July 2024

TPS3168 Background: VIP236, a first-in-class SMDC, consists of an αvβ3 integrin small molecule binder, a peptide linker cleaved by neutrophil elastase (NE) in the tumor microenvironment (TME), and a camptothecin (CPT) payload VIP126 which was optimized for high permeability and low efflux. The overall drug design strategy for VIP236 is targeted delivery to the TME and tumors expressing αVβ3 integrin on their cell surface with release of the optimized CPT derivative by NE also present in the TME. VIP126, when delivered as a component of VIP236, is anticipated to kill tumor cells while reducing effects to normal tissue. VIP236 exhibits convincing single agent in vivo antitumor efficacy and acceptable tolerability in multiple human tumor cell line- and patient- derived xenograft models in mice, including breast, colorectal, small cell lung, gastric, metastatic breast and metastatic colon cancer. In three gastric cancer xenograft models, VIP236 caused statistically significant tumor growth inhibition across the models independent of HER2 status. VIP236 outperformed an anti-HER2 ADC, trastuzumab deruxtecan, in all three models. Methods: This trial in progress is an open-label, global, multicenter Phase 1 study to characterize safety, tolerability, preliminary antitumor activity and pharmacokinetics of VIP236 monotherapy in subjects with advanced cancer. Enrollment includes all comer patients with histologically confirmed advanced or metastatic solid tumors that are relapsed or refractory to standard of care. Subjects must have exhausted all available standard therapies or be deemed ineligible for potential available therapies. Frequency, severity, and relationship to study drug of any treatment-emergent adverse events or abnormalities of laboratory tests will be studied. Tumor response will be assessed using RECIST 1.1 criteria. The following dose schedules are being evaluated: 1) Cohorts 1, 2a, and 3a: A cycle is 21 days 1-hour intravenous (IV) infusions on a 2 days on/5 days off schedule with no pause between cycles. 2) Cohorts 2b, 3b, 4b, 5b, 6b, 7b, and 8b: A cycle is 21 days of VIP236 given as a 1-hour IV infusion once every three weeks (Q3W) with no pause between cycles. 3) Cohorts 1, 2a, 3a, 2b, 3b and 4b have been completed. Enrollment continues in the Q3W cohorts. Clinical trial information: NTC05371054.