On June 5, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported the preliminary data of IBI351 (GFH925) (KRASG12C inhibitor) from dose escalation portion of a phase I clinical trial (NCT05005234) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Innovent Biologics, JUN 5, 2022, View Source [SID1234615592]).

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Phase I dose-escalation study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors

Poster Presentation, Abstract #: 3110

IBI351(GFH925) is a novel, irreversible covalent inhibitor of KRASG12C mutation. The NCT05005234 study presented was a first-in-human study conducted in China to evaluate the safety, tolerability and efficacy of IBI351 monotherapy in patients with advanced solid tumors who failed or intolerant to standard of care treatment. As data cutoff (15 April 2022), 31 subjects were enrolled in the study, including 25 patients with non-small cell lung cancer, 5 colorectal cancer and 1 pancreatic cancer. Approximately 30% patients received 3 lines or above prior systemic anticancer therapy. The highlights of the study results were as follows:

Of 21 patients (including 16 non-small cell lung cancer and 5 colorectal cancer) having at least 1 tumor assessment per RECISTv1.1, 9 achieved PR, with investigator assessed ORR 42.9% and DCR 81%.
Of 12 patients with NSCLC treated at/above doses of 700mg once daily, 6 achieved PR, with investigator assessed ORR 50% and DCR 83.3%.
Of 5 CRC patients, 2 achieved PR, with investigator assessed ORR 40% and DCR 60%.
As data cutoff, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 93.5% (29/31) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, vomiting and diarrhea. The majority of the TRAEs were grade 1-2 with 12.9% (4/31) of patients reporting grade 3 TRAEs. There were no grade 4-5 TRAEs or TRAEs led to treatment discontinuation.
Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed in previously-treated advanced non-small cell lung cancer and colorectal cancer harboring KRASG12C mutation. As data cutoff, dose escalation is still ongoing. More data will be presented at the future medical meeting.

Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, stated: "KRASG12C mutation occurs in about 2~4% of non-small cell lung cancer and 2.5% of colorectal cancer in China, and no KRASG12C inhibitor was approved yet in China. IBI351 is a novel, irreversible covalent inhibitor of KRASG12C mutation. The preliminary data shows the favorable safety and promising activity of IBI351 (GFH925) monotherapy in KRAS G12C mutated advanced solid tumor. We look forward to more positive clinical data from this study. "

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present our clinical development updates at the 2022 ASCO (Free ASCO Whitepaper), and that IBI351 monotherapy demonstrated encouraging efficacy and safety data in phase I dose-escalation study. We are working to advancing into late stage clinical development to explore the potential of IBI351 in monotherapy and combo-therapy. We hope to benefit more cancer patients as we are exploring next-generation immunotherapies."

To learn more about Innovent’s R&D updates and activities at 2022 ASCO (Free ASCO Whitepaper), please visit View Source

About IBI351/GFH925 (KRASG12C Inhibitor)

Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards G12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest. In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.

On June 5, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that clinical data of IBI110 (anti-LAG-3 monoclonal antibody) from three clinical trials will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held June 3-7, 2022 (Press release, Innova Therapeutics, JUN 5, 2022, View Source [SID1234615591]). This includes clinical data from a Phase Ia/Ib clinical study and preliminary results from two Phase Ib Proof-of-Concept (PoC) clinical studies for the treatment of advanced squamous non-small cell lung cancer (sqNSCLC) and advanced gastric cancer (GC).

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IBI110 (anti-LAG-3 mAb) as a single agent or in combination with sintilimab (anti-PD-1 mAb) in patients with advanced solid tumors: updated results from the Phase Ia/Ib dose-escalation study

Poster Presentation, Abstract #: 2650

This is a first-in-human, Phase Ia/Ib study of IBI110 in patients with advanced solid tumors, including Phase Ia IBI110 monotherapy and Phase Ib combination therapy of IBI110 and sintilimab. The highlights for the study results were as follows:

39 patients with advanced solid tumors who failed standard of care therapy were treated with IBI110 (≥ 3 mg/kg) in combination with sintilimab and received at least 1 post-baseline tumor assessment. 6 patients achieved partial response (PR); the objective response rate (ORR) was 15.4% and the disease control rate (DCR) was 64.1%.
31 patients with advanced NSCLC who failed standard of care, and 6 patients achieved PR; the ORR and DCR were 19.4% and 74.2%, respectively.
For safety results, no dose limiting toxicity (DLT) was observed in either Phase Ia or Ib dose escalation. In Phase Ib dose escalation, treatment-related adverse events (TRAEs) occurred in 75.6% (34/45) patients, most of which were grade 1-2, and the most common TRAEs were aspartate aminotransferase increased (28.9%), anemia (24.4%) and alanine aminotransferase increased (22.2%).
Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) in first-line advanced squamous non-small cell lung cancer (sqNSCLC): initial results from a Phase Ib study

Abstract #: e21145

In this Phase Ib study, the efficacy and safety of IBI110 in combination with sintilimab as first-line therapy for advanced sqNSCLC was evaluated.

20 untreated advanced sqNSCLC patients received 200 mg IBI110 combined with sintilimab and chemotherapy and received at least 1 post-baseline tumor assessment. As of the data cutoff date of Jan 20, 2022, 16 patients achieved PR, the ORR was 80%. The study is still ongoing and will continue to monitor depth of response overtime.
For safety results, the most common TRAEs ≥ grade 3 were neutrophil count decreased (30%) and white blood cell count decreased (20%). Immune-related AEs occurred in 11 patients (55%) and most were grade 1-2. There were no treatment-related deaths or TRAEs led to treatment discontinuation.
IBI110 alone or plus sintilimab indicate a manageable safety profile andpromising antitumor activity from the preliminary data. The study is ongoing with the clinical data in squamous NSCLC is continuing to mature and will be presented in the future.
Efficacy and safety of IBI110 in combination with sintilimab in first-line advanced HER2-negative gastric cancer or gastroesophageal junction cancer: preliminary results from a Phase Ib study

Abstract #: e16097

In this Phase Ib study, the efficacy and safety of IBI110 in combination with sintilimab as first-line therapy for advanced GC was evaluated.

15 untreated advanced GC patients received 200 mg IBI110 combined with sintilimab and chemotherapy and received at least 1 post-baseline tumor assessment. At the cut-off date of January 20, 2022, 9 patients achieved PR; the ORR and DCR were 60% and 100%, respectively. Up to the press release date, the ORR reached 76.5% and most patients were still in treatment.
The most common TRAEs ≥ grade 3 were neutrophil count decreased (11.1%), platelet count decreased (11.1%) and hepatic function abnormal (11.1%). Immune-mediated AEs occurred in 7 pts (38.9%). One patient discontinued treatment due to coronary artery disease. There were no treatment-related deaths.
Professor Caicun Zhou, Shanghai Pulmonary Hospital, stated: "Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, of which non-small cell lung cancer accounts for about 80%. In recent years, PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer. However, persistent response to immune checkpoint inhibitor monotherapy remains a challenge in clinical practice. IBI110 plus sintilimab indicate a manageable safety profile and promising antitumor activity in untreated squamous non-small cell lung cancer patients. The ORR reached 80%, suggesting that it is worth further exploring the safety and efficacy of IBI110 combination therapy in this indication."

Professor Nong Xu, The First Affiliated Hospital, School of Medicine, Zhejiang University, stated: "Immune checkpoint inhibitors have shown good efficacy in a variety of tumors, but clinical challenges still remain. A key part of the mechanism of action is the synergistic inhibition of LAG-3 and PD-1 could have the potential to enhance the immune response and inhibit tumor growth. We are encouraged by the results we’ve seen to date in this study and the potential of this medicine."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present our clinical development updates at the 2022 ASCO (Free ASCO Whitepaper) Meeting. IBI110 in combination with sintilimab demonstrated encouraging efficacy and safety data in sqNSCLC and GC. We will continue to update on PoC data readout for IBI110 in treatment areas such as lung cancer and plan to initiate subsequent pivotal clinical studies. As immunotherapy moves into the next era, we are actively advancing the development of next-generation immune checkpoint inhibitors, among which IBI110 represents a high-potential LAG-3 asset, and we hope it could benefit more patients in need soon."

To learn more about Innovent’s R&D updates and activities at 2022 ASCO (Free ASCO Whitepaper), please visit View Source

About IBI110

IBI110 is an IgG4κ recombinant human anti-LAG-3 monoclonal antibody independently developed by Innovent Biologics (Suzhou). Based on the mechanism of action and preclinical data of IBI110, it is assumed that IBI110 can inhibit the immune checkpoint signaling to achieve anti-tumor effect, which may further improve the efficacy of immunotherapy, overcome the primary drug resistance, and overcome the drug resistance after anti-PD-1 /PD-L1 monoclonal antibody treatment. Based on the urgent clinical needs, Innovent Biologics has carried out clinical studies to explore PK/PD characteristics of IBI110 single drug and combined with sintilimab in human body as well as its efficacy and safety in various advanced tumors. This is the first in human clinical study of IBI110.

On June 5, 2022 Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported that clinical details in poster presentation featuring phase Ib/II study of its Ivonescimab (PD-1/VEGF BsAbs, AK112) in advanced non-small cell lung cancer (NSCLC) at 2022 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Akeso Biopharma, JUN 5, 2022, View Source [SID1234615589]).

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Summary of the clinical results:

AK112 was safe and well tolerated, with no significant difference between squamous NSCLC (SQ-NSCLC) and non-squamous NSCLC (NSQ-NSCLC) patients. The incidence rate of grade 3-4 TRAE was 13.5%, with no TRAE leading to permanent treatment discontinuation.
Among 54 treatment-naïve patients with PD-L1 positive (PD-L1 TPS≥1%) who had at least one post-treatment tumor assessment, the objective response rate (ORR) was 50.0% and disease control rate (DCR) was 96.3%.
Among 50 treatment-naïve patients receiving AK112 >10 mg/kg Q3W, AK112 presented encouraging anti-tumor efficacy in different PD-L1 expression levels:
In patients with PD-L1 positive patients (TPS ≥ 1%), ORR was 60.0% and DCR was 97.1%.
In patients with TPS 1%-49%, ORR was 50.0% and DCR was 95.5%.
In patients with TPS ≥50%, ORR was 76.9% and DCR was 100.0%.
This is a multicenter, phase Ib/II, open-label study of AK112 monotherapy in advanced NSCLC (NCT04900363). As of 4 March, 2022, 96 patients were enrolled, 90 of whom had at least one post-treatment tumor assessment. The dose-selection part was divided into four different dosing regimens including 10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W or 30 mg/kg Q3W, with safety and ORR as the primary endpoints.

Akeso is conducting a phase III study of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III study of AK112 plus chemotherapy versus chemotherapy in EGFR+ advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy (NCT05184712) is ongoing. AK112 has been investigated for different stages of treatment for both NSCLC and small cell lung cancer.

Related Study

KEYNOTE-042 study is a clinical study in patients with PD-L1 positive (TPS ≥ 1%) locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. According to this study, ORR was 27.0% in patients with PD-L1 TPS≥1%) and 39.0% in patients with TPS≥50% in the Pembrolizumab group.[1][2]

Reference

[1] Mok TSK, Wu YL, Kudaba I, et al. KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. doi: 10.1016/S0140-6736(18)32409-7.

[2] Disclaimer: the study mentioned above is for reference only. It doesn’t necessarily represent the latest clinical study ongoing for the same indication, and it is not a head-to-head study derived from AK112 clinical trial.

On June 5, 2022 Akeso, Inc. (9926.HK) ( "Akeso" ), a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology, reported results of Cadonilimab (PD-1/CTLA-4 Bispecific, AK104) combined with platinum-based chemotherapy +/- bevacizumab for the first-line treatment of recurrent/metastatic cervical cancer (R/M CC) (Press release, Akeso Biopharma, JUN 5, 2022, View Source [SID1234615588]). The findings were reported in an oral presentation at 2022 ASCO (Free ASCO Whitepaper) Annual Meeting.

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Summary of the clinical results:

At dose of 10mg/kg, regardless of CPS status, Cadonilimab combined with platinum-based chemotherapy +/- bevacizumab, the objective response rate (ORR) was 79.3%; in CPS≥1 and CPS<1 population, ORR was 82.4% and 75.0%, respectively. Progression-free survival (PFS) or overall survival (OS) data is not mature by the cut-off date.
Among all evaluable patients treated with the 10 mg/kg dose, 41.4% of the patients were PD-L1-negative patients (CPS<1)
The incidence of ≥3 grade TRAE of the trial was 60.0%.
As of April 18, 2022, the study evaluated the safety of all patients and the efficacy of patients who received at least one tumor evaluation. The results of Cadonilimab combined with platinum-based chemotherapy +/- bevacizumab continued the excellent performance of Cadonilimab monotherapy for second-or third-line R/M CC and demonstrating a promising therapeutic solution for all patients with advanced cervical cancer.

Based on the excellent efficacy and safety results of phase II study, Akeso is conducting a phase III study of Cadonilimab plus platinum-based chemotherapy +/- bevacizumab in first-line treatment for R/M cervical cancer. In September 2021, Akeso submitted NDA in China for Cadonilimab for the treatment of second-or third-line R/M CC under priority review. In addition, a phase III study of Cadonilimab plus concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) is also ongoing.

Related Study

FDA has approved Pembrolizumab plus chemotherapy +/- bevacizumab for first-line treatment of persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test (KEYNOTE-826 study). According to the KEYNOTE-826 study, in the Pembrolizumab arm, ORR was 65.9% in the all-comer population and 68.1% in the CPS≥1 population, the percentage of patients with CPS <1 was 11.4%, the incidence of ≥3 grade TRAE was 68.4%. In the placebo arm (placebo plus chemotherapy +/- bevacizumab), ORR was 50.2% in the CPS≥1 population.[1][2]

Reference

[1] Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. doi: 10.1056/NEJMoa2112435.

[2] Disclaimer: the study mentioned above is for reference only. It doesn’t necessarily represent the latest clinical study ongoing for the same indication, and it is not a head-to-head study derived from Cadonilimab clinical trial.

On June 5, 2022 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that yesterday on June 4, 2022, in the Industry Expert Theater during the ASCO (Free ASCO Whitepaper) 2022 conference, Dr. Marnix Bosch made a presentation discussing the Company’s DCVax-L technology for personalized dendritic cell vaccines, the Sawston, UK facility, the manufacturing technology, the development of automation, and preparations for manufacturing scale-up (Press release, Northwest Biotherapeutics, JUN 5, 2022, View Source [SID1234615587]). In addition, a video presentation about the DCVax-L clinical program was screened in the Company’s exhibit booth in the ASCO (Free ASCO Whitepaper) Exhibit Hall.

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These presentations are now available online at View Source

The Industry Expert Theater is not an official event of the ASCO (Free ASCO Whitepaper) Annual Meeting. It is not sponsored, endorsed or accredited by ASCO (Free ASCO Whitepaper), CancerLinq, or Conquer Cancer the ASCO (Free ASCO Whitepaper) Foundation. It is not CME-accredited.