Delving into the Latest Updates on Reozalimab with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

+ [2]

Target

PD-1 x PDL1

Mechanism

PD-1 inhibitors(Programmed cell death protein 1 inhibitors), PDL1 inhibitors(Programmed death-ligand 1 inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Small Cell Lung CancerAdvanced cancer

Inactive Indication

Advanced Malignant Solid NeoplasmAdvanced Skin Squamous Cell CarcinomaCutaneous Squamous Cell Carcinoma+ [2]

Originator Organization

Eli Lilly & Co.

Innovent Biologics (Suzhou) Co. Ltd.

Active Organization

Innovent Biologics (Suzhou) Co. Ltd.

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePhase 1

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure/Sequence

Sequence Code 319333906H

Source: *****

Sequence Code 319333900L

Source: *****

Sequence Code 315623394L

Source: *****

Sequence Code 319333897H

Source: *****

The study is a prospective multi-cohort clinical study. Cohort A is evaluating the efficacy and safety of IBI318 in combined with lenvatinib in advanced NSCLC patients who had failed first-line PD-1/PD-L1 inhibitor therapy. Cohort B is the efficacy and safety of advanced NSCLC with EGFR-sensitive mutation /ALK fusion after EGFR-TKI /ALK-TKI treatment resistance. Cohort C is the efficacy and safety of first-line treatment of advanced NSCLC with negative PD-L1 expression and EGFR, ALK, and ROS1 wild-type. After being screened to meet the inclusion criteria, they will receive IBI318 combined with lenvatinib until the disease progresses, death, toxicity is intolerable, informed consent is withdrawn, new anti-tumor therapy is started, or the treatment is terminated for other reasons specified in the plan.

Start Date01 Aug 2021

Sponsor / Collaborator

Hunan Cancer Hospital

CTR20202318

/ TerminatedPhase 1

IBI318联合常规TACE（cTACE）围手术期治疗潜在可切除的肝细胞癌安全性和有效性的Ib期研究

[Translation] A Phase Ib Study on the Safety and Efficacy of IBI318 Combined with Conventional TACE (cTACE) in the Perioperative Treatment of Potentially Resectable Hepatocellular Carcinoma

比较IBI318联合cTACE对比安慰剂联合cTACE围手术期治疗潜在可切除肝细胞癌的安全性和耐受性

[Translation]

Comparison of the safety and tolerability of IBI318 plus cTACE versus placebo plus cTACE in the perioperative treatment of potentially resectable hepatocellular carcinoma

Start Date25 Dec 2020

Sponsor / Collaborator

Innovent Biologics (Suzhou) Co. Ltd.

NCT04635527

/ TerminatedPhase 1

A Phase Ib Study to Evaluate the Safety and Efficacy of IBI318 Combined With Conventional TACE (cTACE) as a Perioperative Treatment for Potentially Resected Hepatocellular Carcinoma

The purpose of this phase Ib study is to assess the safety, tolerability and effectiveness of IBI318 in combination with conventional TACE (cTACE) in patients with potentially resected hepatocellular carcinoma.

Start Date24 Dec 2020

Sponsor / Collaborator

Innovent Biologics (Suzhou) Co. Ltd.

100 Clinical Results associated with Reozalimab

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100 Translational Medicine associated with Reozalimab

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100 Patents (Medical) associated with Reozalimab

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3

Literatures (Medical) associated with Reozalimab

01 Oct 2020·Cancer Immunology ResearchQ1 · MEDICINE

Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity

Q1 · MEDICINE

Article

Author: Chin, Darin ; Torgerson, Stacy ; Kotanides, Helen ; Shen, Yang ; Wang, George ; Eastman, Scott W. ; Novosiadly, Ruslan D. ; Surguladze, David ; Han, Bing ; Topper, Michael ; Pennello, Anthony L. ; Li, Yiwen ; Hindi, Sagit ; Carpenito, Carmine ; Malabunga, Maria ; Moxham, Christopher M. ; Inigo, Ivan ; Chen, Xinlei ; Bailey, Tim ; Kalos, Michael ; Plowman, Gregory D. ; Lao, Yanbin ; Ludwig, Dale L. ; Persaud, Krishnadatt ; Zhang, Yiwei ; Haidar, Jaafar N. ; Bulaon, Danielle K. ; Sonyi, Andreas

AbstractThe programmed cell death protein 1 receptor (PD-1) and programmed death ligand 1 (PD-L1) coinhibitory pathway suppresses T-cell–mediated immunity. We hypothesized that cotargeting of PD-1 and PD-L1 with a bispecific antibody molecule could provide an alternative therapeutic approach, with enhanced antitumor activity, compared with monospecific PD-1 and PD-L1 antibodies. Here, we describe LY3434172, a bispecific IgG1 mAb with ablated Fc immune effector function that targets both human PD-1 and PD-L1. LY3434172 fully inhibited the major inhibitory receptor–ligand interactions in the PD-1 pathway. LY3434172 enhanced functional activation of T cells in vitro compared with the parent anti–PD-1 and anti–PD-L1 antibody combination or respective monotherapies. In mouse tumor models reconstituted with human immune cells, LY3434172 therapy induced dramatic and potent antitumor activity compared with each parent antibody or their combination. Collectively, these results demonstrated the enhanced immunomodulatory (immune blockade) properties of LY3434172, which improved antitumor immune response in preclinical studies, thus supporting its evaluation as a novel bispecific cancer immunotherapy.

Frontiers in Oncology

Octreotide plus IBI-318 plus anlotinib in the treatment of multiple neuroendocrine metastases of unknown primary lesions: a case report

Article

Author: Zhang, Yuda ; Zeng, Liang ; Chen, Yangqian ; Xiang, Siqi ; Zhang, Yongchang ; Yan, Huan ; Zhang, Xing ; Huang, Zhe ; Qin, Haoyue ; Yang, Nong

BackgroundThe second-line treatment of neuroendocrine tumors (NETs) of unknown primary origin remains uncertain. This report presented a patient who received octreotide plus IBI-318 plus anlotinib as a second-line treatment for multiple metastatic NETs of unknown primary lesions after the failure of octreotide plus everolimus.Case presentationA 32-year-old male patient presented with elevated CEA (197.83 ng/ml) without specific symptoms. A contrast-enhanced computed tomography (CT) scan showed multiple metastatic lymph nodes and multiple low-density nodules in the liver of undetermined nature. A right supraclavicular lymph node biopsy indicated NET, but the primary tumor origin remained unknown. PD-L1 expression was negative in tumor tissue according to immunohistochemistry. Immunofluorescence indicated the CD4+ T cells, CD8+ T cells, and Treg cells were gathered around blood vessels, with only a few infiltrating lymphocytes in the tumor tissue. Treatment with octreotide (30 mg/28 d) plus everolimus (5 mg qd) led to disease progression after three cycles. Treatment was changed to octreotide (30 mg/28 d) plus IBI318 (400 mg/28 d) plus anlotinib (10 mg/1-14 d/q3w), leading to partial remission, which was sustained up to the last follow-up (June 20, 2023), with a PFS of 11 months. The patient experienced no treatment-related adverse reactions.ConclusionsOctreotide plus IBI318 plus anlotinib achieved benefits in a patient with advanced NETs of unknown primary lesions after first-line treatment failure, even though with low PD-L1 expression. This case suggests that combining SSAs, TKIs and PD-1/PD-L1 inhibitors could be an alternative second-line treatment for patients with advanced, well-differentiated NETs.

Journal of Hematology & Oncology

The first-in-class bispecific antibody IBI318 (LY3434172) targeting PD-1 and PD-L1 in patients with advanced tumors: a phase Ia/Ib study

Article

Author: Liu, Fu-Rong ; Zhao, Yan-Qiu ; Huang, Ding-Zhi ; Ji, Dong-Mei ; Wei, Xiao-Li ; Xu, Nong ; Xu, Rui-Hua ; Lu, Xiao-Xiao ; Pan, Hong-Min ; Zhang, Jian ; Chen, Yu-Ling ; Zhao, Hong-Yun ; Zhang, Wen ; Yang, Kun-Yu ; Liao, Wang-Jun ; Hu, Xi-Chun ; Ruan, Dan-Yun ; Zhou, Hui

BACKGROUNDThere is an unmet clinical need to enhance the response rate and safety of anti-PD-1/PD-L1-based cancer immunotherapy (IO). Herein, we presented the clinical study of IBI318 (LY3434172), a first-in-class bispecific antibody (bsAb) targeting PD-1 and PD-L1, in patients with advanced tumors.METHODSIn this open-label, multicenter Phase Ia/Ib study of IBI318, the Phase Ia involved dose escalation and a safety dose expansion, while the Phase Ib focused on preliminary safety and efficacy evaluation in non-small cell lung cancer (NSCLC) and nasopharyngeal carcinoma (NPC). In Phase Ia, patients with advanced tumors received IBI318 doses ranging from 0.3 to 1200 mg every two weeks (Q2W) to determine the recommended Phase 2 dose (RP2D). In Phase Ib, NSCLC or NPC patients from five cohorts with varying treatment histories received IBI318 at the RP2D. The primary endpoint was safety and the secondary endpoints included efficacy assessed by investigators according to RECIST v1.1, pharmacokinetics, immunogenicity, and pharmacodynamics.RESULTSFrom February 11, 2019, to January 25, 2022, a total of 103 eligible patients were enrolled (Phase Ia, n = 55; Phase Ib, n = 48). The median follow-up was 10.1 months (range 0.7-28.6). The RP2D was determined to be 300 mg Q2W. Treatment-related adverse events (TRAEs) of any grades occurred in 88 patients (85.4%), while 10 patients (9.7%) experienced grade ≥ 3 TRAEs. The objective response rate (ORR) was 15.5% and the disease control rate (DCR) was 49.5% in all patients. In Phase Ib, the confirmed ORR was 45.5% in treatment-naïve NSCLC patients and 30.0% in IO-naïve NPC patients who had failed or were intolerant to platinum-based treatments.CONCLUSIONSIBI318 demonstrated a favorable safety profile and preliminary efficacy in treatment-naïve NSCLC and IO-naïve NPC patients. Further clinical studies are needed to assess the full therapeutic potential of PD-1/PD-L1 dual inhibition with bsAbs.

100 Deals associated with Reozalimab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cutaneous Squamous Cell Carcinoma	Phase 2	CN	Innovent Biologics (Suzhou) Co. Ltd.	01 Dec 2020
Advanced Malignant Solid Neoplasm	Phase 2	KR	Eli Lilly & Co.	24 May 2019
Advanced Malignant Solid Neoplasm	Phase 2	BE	Eli Lilly & Co.	24 May 2019
Advanced Malignant Solid Neoplasm	Phase 2	US	Eli Lilly & Co.	24 May 2019
Advanced Malignant Solid Neoplasm	Phase 2	AU	Eli Lilly & Co.	24 May 2019
Advanced Malignant Solid Neoplasm	Phase 2	FR	Eli Lilly & Co.	24 May 2019
Small Cell Lung Cancer	Phase 1	CN	Innovent Biologics (Suzhou) Co. Ltd.	14 Dec 2020
Advanced cancer	Phase 1	CN	Innovent Biologics (Suzhou) Co. Ltd.	01 Apr 2019
Advanced Skin Squamous Cell Carcinoma	Discovery	CN	Innovent Biologics (Suzhou) Co. Ltd.	19 Nov 2020
Extranodal NK-T-Cell Lymphoma	Discovery	CN	Innovent Biologics (Suzhou) Co. Ltd.	03 Nov 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03936959 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm \| Advanced cancer	10	LY3434172 (30 mg LY3434172)	whalzltfyy(cassruefkh) = mfryqmufnk mofcjlexzn (csocthdxrp, epiglwbheo - ihjygcqkhz) View more	-	15 Jan 2025
NCT03936959 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm \| Advanced cancer	10	LY3434172 (100 mg LY3434172)	whalzltfyy(cassruefkh) = xpcenewtpx mofcjlexzn (csocthdxrp, ervnjzauhq - orotgqtzcf) View more	-	15 Jan 2025
NCT03875157 (ASCO 12020 \| ASCO 22020) Manual	Phase 1	Neoplasms Second line	15	Reozalimab	(xgtkbkxrra) = no DLT from 0.3mg to 300mg group tvbieuqson (pozjndnaap ) View more	Positive	29 May 2020