BACKGROUND:This first-in-human clinical study explored lomvastomig, an immunoglobulin G1-based Fc-silenced bispecific antibody that simultaneously blocks the immune checkpoint receptors programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain-3. METHODS:Lomvastomig was characterized in cell cultures and preclinically in cancer mouse models. The phase 1, open-label, multicenter clinical study of lomvastomig included a dose-escalation part in patients with advanced and/or metastatic solid tumors and an expansion part with four tumor-specific cohorts, which enrolled checkpoint inhibitor (CPI)-experienced patients with melanoma and non-small-cell lung cancer (NSCLC) and CPI-naïve patients with SCLC and esophageal squamous cell carcinoma (ESCC). Primary and secondary objectives included safety/tolerability, maximum tolerated dose (MTD)/recommended dose for expansion (RDE), pharmacokinetics, drug receptor occupancy, and antitumor activity. RESULTS:39 and 95 patients were enrolled in the dose-escalation and expansion parts, respectively. Lomvastomig was well tolerated up to the highest tested dose of 2,100 mg every 2 weeks (Q2W). One dose-limiting toxicity was reported at 1,200 mg (grade 3 troponin T increase). No MTD was reached, and 2,100 mg Q2W was established as the RDE. Linear pharmacokinetics across the studied dose range suggested target saturation. Peripheral blood drug receptor occupancy on CD3+ and CD8+ was saturated at >90% throughout treatment for doses ≥70 mg. Objective responses were observed at 2,100 mg lomvastomig during dose-escalation (21%; n=19), and in the CPI-experienced melanoma (8%, n=38) and CPI-naïve ESCC (20%, n=15) expansion cohorts. CONCLUSIONS:Lomvastomig had a tolerable and manageable safety profile at 2,100 mg Q2W. Clinical activity was limited in CPI-experienced patients with melanoma and NSCLC, while an encouraging signal was observed in CPI-naïve patients with ESCC. TRIAL REGISTRATION NUMBER:NCT03708328 (registration date: 2018-10-09).

Abstract Background: Apoptosis modulation may enhance the efficacy of standard-of-care chemotherapy (CT) and concurrent chemoradiotherapy (cCRT) in solid tumors. BGB-24714, a selective SMAC mimetic that antagonizes Inhibitor of Apoptosis Proteins (IAPs), has demonstrated promising preclinical antitumor activity. This open-label, multicenter, first-in-human Phase (Ph) 1 study evaluated BGB-24714 as monotherapy or in combination with CT or cCRT in patients (pts) with advanced or metastatic solid tumors (NCT05381909). Methods: The study included dose-escalation (1a) and -expansion (1b) Phs. Ph1a Part A assessed BGB-24714 monotherapy; Part B: BGB-24714 + weekly paclitaxel; Parts C/D: BGB-24714 + cCRT in NSCLC and esophageal squamous cell carcinoma (ESCC), respectively. Ph1b enrolled pts with second-line or later metastatic NSCLC and platinum-resistant ovarian cancer (PROC) to receive BGB-24714 + docetaxel or paclitaxel, respectively. Primary endpoints were safety/tolerability (Ph1a) and preliminary antitumor activity (Ph1b). Results: As of July 25, 2025, 157 pts were enrolled and treated (132 in Ph1a; 25 in Ph1b [11 NSCLC; 14 PROC]). 9 dose levels (DLs; 30 mg to 900 mg QD) of BGB-24714 were assessed (n=68) in Ph1a Part A and 7 DLs (60 mg to 650 mg QD) in Ph1a Parts B to D (n=64). No MTD was reached in Ph1a monotherapy or combination dose escalation.The most common BGB-24714-related TEAEs varied by study part and were predominantly low grade: nausea (33.8%) in Ph1a Part A, diarrhea (25%) in Part B, neutrophil count decreased (43.8%) in Parts C/D, diarrhea and fatigue (45.5% each) in Ph1b-NSCLC, and stomatitis, ALT/AST increased (28.6% each) in Ph1b-PROC. The most common Grade ≥3 BGB-24714-related TEAEs were ALT increased (5.9%) in Ph1a Part A, lipase increased and fatigue (6.3% each) in Part B, neutrophil count decreased (31.3%) in Parts C/D, anemia (27.3%) in Ph1b-NSCLC, and neutrophil count decreased (28.6%) in Ph1b-PROC. The most common serious BGB-24714-related TEAEs (≥5%) were pneumonitis (6.3%) in Ph1a Part B, diarrhea (18.2%) in Ph1b-NSCLC, and febrile neutropenia and fatigue (7.1% each) in Ph1b-PROC. Treatment discontinuation due to BGB-24714-related TEAEs occurred in 12.1% of Ph1a and 24.0% of Ph1b pts. Confirmed ORRs in Ph1a were 0% (Part A), 12.8% (Part B), 54.5% (Part C), and 66.7% (Part D); DCRs were 40.0%, 59.6%, 81.8%, and 100.0%, respectively. In Ph1b, confirmed ORRs were 0% in NSCLC and 28.6% in PROC; DCRs were 70.0% and 85.7%, respectively; median PFS was 162 days for both NSCLC and PROC. Pharmacodynamics showed rapid and sustained cIAP1 degradation in a dose-dependent manner, demonstrating strong target engagement in apoptosis regulatory pathway. Conclusion: BGB-24714 demonstrated antitumor activity with a manageable safety profile in pts with advanced or metastatic solid tumors. Citation Format: Andreas Varkaris, Erika Hamilton, Jermaine Coward, Rafael Santana-Davila, Jinming Yu, Byoung Chul Cho, Jung Yun Lee, Yongsheng Li, Sanjeev Deva, Youngjoo Lee, Huai Liu, Yuping Sun, Zhe Yang, Wen Xu, Sook Ryun Park, Se-Hoon Lee, Andrew Z. Wang, Hui Shao, Jinhui Zhang, Zhaoyin Zhu, Runzhe Chen, Hua-Xin Gao, Judy S. Wang. A phase 1 study of BGB-24714, a second mitochondrial-derived activator of caspases (SMAC) mimetic, as monotherapy or in combination with chemotherapy or concurrent chemoradiotherapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT120.

Inherited dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for severe 5-fluorouracil toxicity. We report a phenotyping approach (thymine challenge test) to prospectively determine DPD activity and the association with severe adverse events. The primary aim of this prospective study was to determine whether a thymine challenge test could prospectively identify patients at risk of severe toxicity from treatment with 5-fluorouracil/capecitabine in combination chemotherapy schedules or monotherapy. The focus was prediction of those at risk of ≥ grade 3 gastrointestinal toxicity. DPD activity was determined from the thymine/dihydrothymine (THY/DHT) ratio measured in a urine sample after a thymine test dose (250 mg, oral). Of the 166 patients, 11.7

Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and promising antitumor activity in patients with advanced KRAS G12C-positive non-small cell lung cancer (NSCLC). Here, we report long-term (≥1 year) follow-up of single-agent divarasib from the ongoing, open-label, and multicenter phase I study (ClinicalTrials.gov identifier: NCT04449874). The primary objective was safety, and the other objectives included preliminary antitumor activity. Overall, 65 patients with advanced KRAS G12C-positive NSCLC received single-agent oral divarasib 50-400 mg once daily and 31 patients (48%) were treated beyond 1 year. Divarasib continued to be well tolerated, and the safety profile beyond 1 year was consistent with the overall safety profile. In patients with measurable disease at baseline across all dose levels (n = 63), the confirmed objective response rate was 55.6% (95% CI, 42.5 to 68.1), and the median duration of response was 18.0 months (95% CI, 11.1 to 24.9). The median progression-free survival was 13.8 months (95% CI, 9.8 to 25.4) in the overall population (N = 65) and 15.3 months (95% CI, 12.3 to 26.1) among patients assigned to the 400-mg dose level (n = 44). With extended follow-up, divarasib demonstrated long-term safety and antitumor activity in patients with advanced KRAS G12C-positive NSCLC.

OX40 may stimulate T-cell activation, potentially enhanced with checkpointinhibition. Results are from the dose-escalation part of an ongoing, multicenter, open-label study (NCT04215978, registered 30 December 2019) investigating OX40 agonist BGB-A445 alone or with anti-PD-1 antibody tislelizumab in patients with advanced solid tumors. Adults ≥18 years with previously treated advanced solid tumors, measurable by RECIST v1.1, enrolled. Dose-escalation A: 8 cohorts received increasing doses of IV BGB-A445 as monotherapy (20, 60, 150, 300, 600, 1200, 2400, 3600 mg); dose-escalation B: 6 cohorts received increasing doses of IV BGB-A445 (150, 300, 600, 1200, 2400, 3600 mg) + IV tislelizumab 200 mg. Primary objectives were safety and tolerability; secondary objectives included overall response rate (ORR) and pharmacokinetics. 112 patients were treated (A, n=63; B, n=49); 34/112 (30.4

Divarasib (GDC-6036), an oral, highly potent, and selective next-generation KRAS G12C inhibitor (KRAS G12Ci), has shown encouraging clinical activity and tolerability as a single agent in patients with KRAS G12C-positive NSCLC. In pre-clinical models, SHP2 inhibition increases KRAS-GDP occupancy and enhances the antitumor activity of KRAS G12C inhibitors. Here, we report clinical safety and activity of combination divarasib and migoprotafib (GDC-1971; SHP2 inhibitor) in patients with NSCLC. As part of an ongoing phase I study (NCT04449874), patients received divarasib 200 mg or 400 mg daily in combination with oral migoprotafib 20, 40, or 60 mg daily, until intolerable toxicity or disease progression. Safety (NCI-CTCAE v5), pharmacokinetics, and preliminary antitumor activity (RECIST v1.1) were assessed. Circulating tumor DNA (ctDNA) analyses were performed at Cycle 1 Day 1 and Cycle 3 Day 1. As of April 1, 2024, a total of 74 patients with NSCLC received combination divarasib and migoprotafib; 48 patients had no prior KRAS G12Ci exposure. Median lines of prior systemic therapy was 2 (range 0-7) and median time on study treatment was 7.2 months (range 0.3-26.0). Overall, 70 (94.6%) patients experienced at least one treatment-related adverse event (TRAE); the most common TRAEs (≥15%) were diarrhea, nausea, vomiting, peripheral edema, increased blood creatine phosphokinase, fatigue, increased amylase, increased aspartate aminotransferase and increased alanine aminotransferase. Grade 3-4 TRAEs occurred in 32 (43.2%) patients, including diarrhea in 11 (14.9%) patients, increased ALT in 4 (5.4%) patients, and pneumonitis, thrombocytopenia, and neutropenia in 3 (4.1%) patients each. There were no Grade 5 TRAEs. TRAEs led to divarasib dose reduction in 23 (31.1%) patients and migoprotafib dose reduction in 32 (43.2%) patients. Divarasib discontinuation due to TRAEs occurred in 2 (2.7%) patients; migoprotafib discontinuations due to TRAEs occurred in 5 (6.8%) patients. The pharmacokinetic profiles of both divarasib and migoprotafib in combination were similar to their respective single-agent profiles. Among the 48 patients who had no prior KRAS G12Ci exposure (all of whom had measurable disease at baseline), the confirmed ORR was 43.8% and the median PFS was 15.2 months (CI 95% 8.4-not estimated). A decline in ctDNA level was observed at Cycle 3 Day 1 upon divarasib plus migoprotafib treatment, similar to single-agent divarasib treatment. Updated data will be presented for patients both with and without prior KRAS G12Ci exposure. Divarasib in combination with migoprotafib demonstrated an acceptable safety profile and preliminary clinical activity in patients with KRAS G12C-positive NSCLC. Jia Luo, Adrian Sacher, Armando Santoro, Luis Paz-Ares, Sanjeev Deva, Hans Prennen, Maria de Miguel, Rafal Dziadziuszko, Scott A. Laurie, Manish R. Patel, Elena Garralda, Gianluca Del Conte, Loes Latten Jansen, Jayesh Desai, Rita De Cassia Costamilan, Patricia LoRusso, Ben Markman, Salvatore Siena, Pierre Freres, Marloes Van Dongen, Eugenio Fernandez, Andres Cervantes, Josiane Mourão Dias, Sergio Azevedo, Kathryn Arbour, Ruth Perets, Se Hyun Kim, Rasha Cosman, Victor Moreno, Matthew G. Krebs, Yoonha Choi, Sandhya Mandlekar, Mark T. Lin, Zhen Shi, Kenneth K. Yau, Julie Chang, Stephanie Royer-Joo, Tomi Jun, Neekesh V. Dharia, Jennifer L. Schutzman, Myung-Ju Ahn. Divarasib plus migoprotafib combination treatment in patients with KRAS G12C-positive non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT022.

2525 Background: BGB-A445 is a monoclonal antibody OX40 agonist that does not compete with the natural OX40 ligand, reducing the likelihood of a hook effect and distinguishing it from other OX40-targeting therapies. Here, we present results from the dose expansion portion of a ph 1, open-label, dose escalation/expansion trial of BGB-A445 in pts with advanced solid tumors (NCT04215978). Ph 1a results were previously presented (Desai et al . J Clin Oncol. 2023). Methods: Previously treated pts with NSCLC (Part A1), HNSCC (Part A2), or NSCLC with PD-L1 ≥50% (Part C) received BGB-A445 monotherapy, while pts with treatment-naïve recurrent/metastatic NPC (Part B) received BGB-A445 combined with tislelizumab and chemotherapy. Primary endpoints included ORR per investigator (RECIST v1.1); secondary endpoints were to assess PFS, DOR and DCR, safety/tolerability, PK, and host immunogenicity. Results: As of Sep 25, 2024, 54 pts were enrolled in Part A1, 19 in Part A2, 12 in Part B, and 7 in Part C. In the efficacy evaluable analysis set, ORR was 0% in Parts A1, A2, and C, and 70% (7/10; all confirmed PRs, one unconfirmed CR) in Part B. In Parts A1, A2, B, and C, confirmed DCR was 49.0%, 33.3%, 100.0%, and 57.1%, respectively. TEAEs occurred in the majority of pts (Table). The most common treatment-related TEAEs were pyrexia (10.0% [8/80]), chills (5.0% [4/80]), and anemia (5.0% [4/80]) in the monotherapy cohorts, and anemia (75.0% [9/12]), decreased WBC (66.7% [8/12]), decreased neutrophils, and decreased platelets (58.3% [7/12], each) in the combination cohort. Treatment-related serious TEAEs occurred in 2.5% (2/80; pyrexia and asthenia in a single pt each) of pts in the monotherapy cohorts and 8.3% (1/12; febrile neutropenia) in the combination cohort. There were no BGB-A445 or tislelizumab-related TEAEs leading to treatment discontinuation or death. The most common imAE was rash (2.5% [2/80] in the monotherapy cohort; 33.3% [4/12] in the combination cohort). No Gr ≥3 imAEs or IRRs were reported. Conclusions: BGB-A445 alone or in combination with tislelizumab and chemotherapy was generally well tolerated across all doses in pts with advanced NSCLC, HNSCC, and NPC, and showed preliminary antitumor activity. Clinical trial information: NCT04215978 . Safety. Part A1NSCLC(N=54) Part A2HNSCC(N=19) Part BNPC(N=12) Part CNSCLC and PD-L1 ≥50%(N=7) Any treatment-emergent AE 47 (87.0) 16 (84.2) 12 (100.0) 7 (100.0) Gr ≥3 17 (31.5) 5 (26.3) 11 (91.7) 3 (42.9) Serious 21 (38.9) 4 (21.1) 2 (16.7) 4 (57.1) Leading to death 4 (7.4) 2 (10.5) 0 (0) 0 (0) Leading to treatment discontinuation 8 (14.8) 3 (15.8) 2 (16.7) 0 (0) Any treatment-related treatment-emergent AE 28 (51.9) 7 (36.8) 12 (100.0) 3 (42.9) Gr ≥3 1 (1.9) 0 (0) 11 (91.7) 0 (0) Any immune-mediated AE 6 (11.1) 1 (5.3) 6 (50.0) 1 (14.3) Infusion-related reactions 6 (11.1) 3 (15.8) 3 (25.0) 1 (14.3) Pts with multiple adverse events (AEs) are counted once. All AEs are listed as n (%).

We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR’s potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology.

Background:TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 RAS mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with KRAS-mutant colorectal cancer. Methods:In the interval between completing CRT and pelvic exenteration, patients with resectable KRAS mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF. Immune response was defined as a positive delayed-type hypersensitivity or positive T cell proliferation assay response. Tumour biopsies were analysed for tumour-infiltrating lymphocytes (TILs) and blood for CEA and ctDNA. TILs and tumouroids were cultured, characterised and tested for their killing efficacy. Results:Six patients with rectal cancer were recruited to evaluate TG02. Three patients experienced a total of 16 treatment-related adverse events; all grade 1. Four of the 6 patients (66.7 %) had at least one vaccine-induced TG02 immune response. Flow cytometry analysis showed high proportion of PD-1-expressing TILs in 2 of 3 patient specimens' post-treatment. A partial to near complete pathological response was reported in 4 of 6 patients. Conclusions:This study demonstrated that TG02/GM-CSF was well tolerated and induced a vaccine specific systemic immune response in the majority of patients. Low numbers limit conclusive clinical outcome reporting. High PD-1 expression on post-treatment TILs encourages the addition of an immune checkpoint inhibitor to TG02 and potentially other studies of peptide vaccines in future studies.

Background Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies in a range of immunogenic cancer types. Blocking this pathway with an oral therapy could benefit patients through greater convenience, particularly in combination regimens, and allow flexible management of immune-mediated toxicities.Methods PD-L1 binding activity was assessed in engineered dimerization and primary cell target occupancy assays. Preclinical antitumor activity was evaluated in ex vivo and in vivo human PD-L1-expressing tumor models. Human safety, tolerability, pharmacokinetics, and biomarker activity were evaluated in an open-label, multicenter, sequential dose-escalation study in patients with advanced solid tumors. Biomarkers evaluated included target occupancy, flow cytometric immunophenotyping, plasma cytokine measurements, and T-cell receptor sequencing.Results GS-4224 binding caused dimerization of PD-L1, blocking its interaction with PD-1 and leading to reversal of T-cell inhibition and increased tumor killing in vitro and in vivo. The potency of GS-4224 was dependent on the density of cell surface PD-L1, with binding being most potent on PD-L1–high cells. In a phase 1 dose-escalation study in patients with advanced solid tumors, treatment was well tolerated at doses of 400–1,500 mg once daily. Administration of GS-4224 was associated with a dose-dependent increase in plasma GS-4224 exposure and reduction in free PD-L1 on peripheral blood T cells, an increase in Ki67 among the PD-1-positive T-cell subsets, and elevated plasma cytokines and chemokines.Conclusions GS-4224 is a novel, orally bioavailable small molecule inhibitor of PD-L1. GS-4224 showed evidence of expected on-target biomarker activity, including engagement of PD-L1 and induction of immune-related pharmacodynamic responses consistent with PD-L1 blockade.Trial registration number NCT04049617.

BACKGROUND:Simlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721). METHODS:Patients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment. FINDINGS:Forty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0-41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4-54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). Median progression-free survival was 3.7 months (95% CI 3.3-9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed. INTERPRETATION:FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC. FUNDING:F. Hoffmann-La Roche Ltd.

Study representation of under-served communities

Duration of most common AEs (reported in ≥20% of patients)

2585 Background: Hematopoietic progenitor kinase 1 (HPK1), a critical negative feedback regulator of T-lymphocyte and dendritic cell activation, is a potential target for IO treatment (tx). BGB-15025, a potent, selective, small-molecule HPK1 inhibitor, showed preliminary antitumor effects in preclinical studies as monotherapy (mono tx) and enhanced antitumor effects in combination with TIS. We present dose-escalation results from an open-label, multicenter, phase 1 study (NCT04649385) of BGB-15025 mono tx and in combination with TIS in pts with advanced solid tumors. Methods: Eligible pts (≥18 yrs) with previously treated (pts with prior exposure to CPIs were eligible) locally advanced/metastatic solid tumors and ECOG PS ≤1 were enrolled. Oral BGB-15025 mono tx was escalated through 7 doses (20 mg QD–240 mg BID); 5 doses (60 mg QD–240 mg QD) were given in combination with TIS 200 mg IV Q3W (combo tx). Primary objectives were assessment of safety and tolerability, determination of the maximum tolerated/administered dose (MTD/MAD) and recommended dose(s) for expansion (RDFE) for mono tx or combo tx. Select secondary and exploratory objectives included preliminary antitumor activity, PK, and PD. Results: As of Nov 21, 2023, 60 and 49 pts received mono tx and combo tx, respectively (median age: 59.0 yrs and 62.0 yrs; median follow-up: 2.3 months and 2.8 months). Most pts were male (56.7% [mono tx]; 67.3% [combo tx]) and received a median of 2 lines of systemic therapy in the metastatic setting (range: 0–7 [mono tx]; 0–5 [combo tx]). The most common tumors were RCC, NSCLC, cervical cancer, CRC, GC/GEJC, and HNSCC. The most common TRAEs (Table) for mono tx were diarrhea (18.3%), vomiting (15.0%), and blood creatinine increased (15.0%); and for combo tx were nausea (30.6%), diarrhea (28.6%), and fatigue (20.4%). No DLTs were observed with mono tx. 5 DLTs were observed with combo tx (2 ALT/AST increased, 1 colitis, 1 immune-related hepatitis, 1 GGT increased). The MAD was 200 mg BID for mono tx and MTD was 150 mg QD for combo tx. For mono tx, there were no responders and disease control rate (DCR) was 35.0%; 3 pts remained on tx for >6 months (2 pts are still on tx for >60 and 84 weeks). For combo tx, the unconfirmed ORR was 18.4% for all doses combined and 31.3% for RDFE, DCR was 57.1% for all doses combined and 56.3% for RDFE. Conclusions: These preliminary results show BGB-15025 mono tx or combo tx with TIS was generally tolerable. The antitumor activity of BGB-15025 was improved when given in combination with TIS. Further investigation of BGB-15025 + TIS +/- chemotherapy is ongoing in the expansion phase. Clinical trial information: NCT04649385 . [Table: see text]

Biomarker analyses and association with clinical outcomes

Abstract Purpose: In this study, we report the results from the esophageal squamous cell carcinoma (SCC) cohort of a phase II, noncomparative, basket study evaluating the antitumor activity and safety of fibroblast activation protein–IL2 variant (FAP-IL2v) plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). Patients and Methods: Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 to 1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor–naïve. Patients received FAP-IL2v 10 mg plus atezolizumab 1,200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks and then every 2 weeks plus atezolizumab 840 mg intravenously every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). Results: In the response-evaluable population (N = 34), the best confirmed ORR was 20.6% [95% confidence interval (CI), 10.4–36.8], with a complete response seen in 1 patient and partial responses in 6 patients. The disease control rate was 44.1% (complete response = 2.9%; partial response = 17.6%; stable disease = 23.5%), and the median duration of response was 10.1 mon/ths (95% CI, 5.6–26.7). The median progression-free survival was 1.9 months (95% CI, 1.8–3.7). Analysis of response by PDL1 expression (Ventana SP263) resulted in an ORR of 26.7% for patients with PDL1-positive tumors (tumor area positivity cutoff ≥1%; n = 15) and 7.1% for patients with PDL1-negative tumors (tumor area positivity cutoff <1%; n = 14). Overall, the treatment combination was tolerable, and adverse events were consistent with the known safety profiles of each drug. Conclusions: FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

Supplementary Figure from Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial