Updated efficacy and safety results from a phase 1b study of the PD-1 antagonist CS1003 combined with lenvatinib (LEN) as first-line (1L) treatment in Chinese patients (pts) with unresectable hepatocellular carcinoma (uHCC).

Shen, Lin; Guo, Ye; Zhang, Yanqiao; Li, Wei; Gong, Jifang; Li, Qun; Ma, Zhi-Gang; Wang, Nanya; Su, Rila; Cai, Zhongheng; Guo, Rong; Li, Peiqi; Tse, Archie

doi:10.1200/jco.2022.40.16_suppl.e16191

Cited by 4 publications

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“…Nofazinlimab in combination with chemotherapy as first-line treatment in patients with extensive-stage small-cell lung cancer and in combination with lenvatinib as first-line treatment in patients with advanced hepatocellular carcinoma are currently being explored in a phase 1a/b study (NCT03809767) in mainland China. Additionally, a phase 3 randomized trial of nofazinlimab plus lenvatinib compared with placebo plus lenvatinib as first-line therapy in patients with advanced hepatocellular carcinoma is ongoing (NCT04194775) based on the promising anti-tumor activity observed in the phase 1 single-arm combination study (NCT03809767) [40,41]. In addition, the combination of nofazinlimab and an anti-CTLA-4 antibody was explored in one phase 1a/1b study (NCT03523819); this combination demonstrated an encouraging anti-tumor activity and favorable safety profile in patients with MSI-H/dMMR tumors, anti-PD-(L)1-refractory melanoma and anti-PD-(L)1-refractory hepatocellular carcinoma [42,43].…”

Section: Discussionmentioning

confidence: 99%

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer

Day,

Park,

Coward

et al. 2023

Br J Cancer

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Background We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). Methods This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1–21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. Results In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. Conclusions Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. Clinical trial registr ation Clinicaltrials.gov (NCT03475251).

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Section: Discussionmentioning

confidence: 99%

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer

Day,

Park,

Coward

et al. 2023

Br J Cancer

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“…Preclinical data show that both CS1002 and CS1003 demonstrated good tolerability in in vivo tests (data not shown). Nofazinlimab monotherapy was well tolerated and demonstrated preliminary antitumor activity in multiple tumortypes 7–9 …”

Section: Introductionmentioning

confidence: 99%

“…Nofazinlimab monotherapy was well tolerated and demonstrated preliminary antitumor activity in multiple tumortypes. [7][8][9] The objective of this study was to investigate the clinical safety, tolerability, preliminary antitumor activity, and pharmacokinetics of CS1002 as monotherapy and in combination with CS1003 in patients with advanced/metastatic solid tumors. Additionally, we aimed to determine the maximum tolerated dose (MTD) and recommended combination dose of CS1002.…”

Section: Introductionmentioning

confidence: 99%

Dual CTLA‐4 and PD‐1 checkpoint blockade using CS1002 and CS1003 (nofazinlimab) in patients with advanced solid tumors: A first‐in‐human, dose‐escalation, and dose‐expansion study

Bishnoi,

Kotasek,

Aghmesheh

et al. 2024

Cancer

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BackgroundThis 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.MethodsThe 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.ResultsParts 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%).ConclusionCS1002, 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.

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Antibodies to watch in 2023

Kaplon

Crescioli

Chenoweth

et al. 2022

mAbs

196

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In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevimab (Beyfortus), mirvetuximab soravtansine (ELAHERE™), and teplizumab (TZIELD)), including 4 bispecific antibodies and 1 ADC. Based on FDA action dates, several additional product candidates could be approved by the end of 2022. An additional seven were first approved in China or Japan in 2022, including two bispecific antibodies (cadonilimab and ozoralizumab). Globally, at least 24 investigational antibody therapeutics are undergoing review by regulatory agencies as of mid-November 2022. Our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline grew by ~20% in the past year to include nearly 140 investigational antibody therapeutics that were designed using a wide variety of formats and engineering techniques. Of those in late-stage development, marketing application submissions for at least 23 may occur by the end of 2023, of which 5 are bispecific (odronextamab, erfonrilimab, linvoseltamab, zanidatamab, and talquetamab) and 2 are ADCs (datopotamab deruxtecan, and tusamitamab ravtansine).

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Updated efficacy and safety results from a phase 1b study of the PD-1 antagonist CS1003 combined with lenvatinib (LEN) as first-line (1L) treatment in Chinese patients (pts) with unresectable hepatocellular carcinoma (uHCC).

Cited by 4 publications

References 0 publications

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer

A first-in-human phase 1 study of nofazinlimab, an anti-PD-1 antibody, in advanced solid tumors and in combination with regorafenib in metastatic colorectal cancer

Dual CTLA‐4 and PD‐1 checkpoint blockade using CS1002 and CS1003 (nofazinlimab) in patients with advanced solid tumors: A first‐in‐human, dose‐escalation, and dose‐expansion study

Antibodies to watch in 2023

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