AACR 2020: Akeso, Gracell Biotech, Hansoh Pharma, and Hengrui Medicine Present Clinical Advances of Novel Therapeutics

At 21:00 (Beijing Time) on April 27, the 111th Annual Meeting of the American Association for Cancer Research (AACR) kicked off in San Diego. Due to the global impact of the COVID-19 pandemic, this year’s AACR Annual Meeting will be held virtually in two sessions. According to publicly available information, Akeso Biopharma, Hansoh Pharma, and Gracell Biotechnologies, among others, will present significant research findings at the conference.

Akeso Biopharma

At this year’s AACR Annual Meeting, preliminary results from the Phase 1b/2 study of Akeso Biopharma’s investigational new drug AK104 in combination with chemotherapy as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma were announced. According to the announcement, AK104 is a globally first-in-class PD-1/CTLA-4 bispecific antibody independently developed by Akeso Biopharma. It is intended for the treatment of multiple cancer types, including cervical cancer, liver cancer, gastric cancer, non-small cell lung cancer, and melanoma, and represents one of the company’s core candidate products.

Data showed that as of April 2, 2020, a total of 19 subjects were evaluable for efficacy. Preliminary efficacy data demonstrated encouraging antitumor activity and a favorable safety profile. Specifically, the objective response rate (ORR) was 57.9% (11/19), and the disease control rate (DCR) was 94.7% (18/19). The longest treatment duration exceeded 42 weeks in some patients, with 13 patients still receiving ongoing treatment. These findings indicate that AK104 in combination with chemotherapy exhibits a favorable safety profile and antitumor efficacy, holding promise as a next-generation cancer immunotherapy superior to PD-1 antibody monotherapy.

Currently, Akeso Biopharma is conducting global clinical trials of AK104 for multiple indications, with the most advanced progress being in cervical cancer. The company expects to submit its first New Drug Application (NDA) to China’s National Medical Products Administration (NMPA) for AK104 in the treatment of cervical cancer in the second half of 2021. Notably, just last Friday, Akeso Biopharma officially listed on the Hong Kong Stock Exchange, raising over USD 300 million and ranking as the top IPO by funds raised on the Hong Kong stock market in 2020.

Hansoh Pharma

Also unveiled at this year’s AACR Annual Meeting was Ameile (almonertinib mesylate tablets), a Class 1 innovative drug independently developed by Hansoh Pharma. In China, more than 40% of lung cancer patients have non-small cell lung cancer (NSCLC) with EGFR gene mutations. After treatment with first-generation EGFR-TKIs, more than half of these patients develop the T790M mutation and acquire drug resistance. There is an urgent clinical need to develop next-generation drugs that are highly efficacious, low in toxicity, and capable of overcoming resistance.

As a third-generation EGFR-TKI, almonertinib mesylate tablets can irreversibly and highly selectively inhibit EGFR-sensitive mutations and T790M resistance mutations. It not only demonstrates favorable efficacy and safety but also shows significant clinical advantages in patients with brain metastases. At this year’s AACR Annual Meeting, the latest Phase II clinical study results of this novel drug in patients with EGFR T790M mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) were disclosed, and efficacy data in patients with brain metastases were reported for the first time.

The report indicates that almonertinib mesylate demonstrates definitive efficacy as a second-line treatment for previously treated EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients, with a median follow-up time of 11.4 months. The overall objective response rate (ORR) was 68.9% (approximately 61% in patients with brain metastases); the overall disease control rate (DCR) was 93.4%, the median progression-free survival (PFS) in the overall population was 12.3 months (approximately 10.8 months in patients with brain metastases), and the median duration of response (DoR) in the overall population was 12.4 months (approximately 11.3 months in patients with brain metastases). In terms of safety, the drug was well tolerated, with drug-related adverse events (AEs) primarily including rash, hepatotoxicity, and anemia. According to the Independent Review Committee assessment, the drug’s efficacy in patients with brain metastases was comparable to that in the overall population, while exhibiting a low incidence of adverse events, no occurrence of interstitial lung disease, and a favorable safety profile.

Notably, almonertinib mesylate was approved by the NMPA for marketing in March this year, for the treatment of adult patients with locally advanced or metastatic disease who have progressed after prior EGFR-TKI therapy and are T790M mutation-positive.

Gracell Biotechnologies

According to Gracell Biotechnologies’ announcement, the company will present Phase I clinical trial data for GC027, developed based on its proprietary TruUCAR™ universal CAR-T platform, at this year’s AACR Annual Meeting. This first-in-human study aims to evaluate the feasibility of treating relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL).

TruUCAR™ is a proprietary patented platform technology exclusive to Gracell Biotechnologies. It edits selected genes on T cells to reduce the risk of graft-versus-host disease (GvHD) and immune rejection without the use of immunosuppressive drugs. According to the announcement, this technology enables allogeneic CAR-T cells to proliferate and persist in patients with human leukocyte antigen (HLA) mismatches, while simultaneously controlling the risk of GvHD.

GC027 utilizes Gracell Biotechnologies’ proprietary TruUCAR™ technology, leveraging healthy donor T cells that do not require HLA matching, making it an off-the-shelf CAR-T cell therapy for the treatment of T-cell malignancies. Data show that one month after receiving GC027 treatment, four patients had no detectable cancer cells in their blood, with two of these patients remaining cancer-free at the six-month follow-up. The fifth patient showed a favorable response at two weeks but experienced relapse shortly thereafter.

In terms of safety, all four patients who achieved a positive response experienced cytokine release syndrome (CRS). This is a severe immune reaction triggered by the widespread attack and elimination of cancer cells by CAR-T immune cells. One patient developed life-threatening CRS, while the other three experienced less severe CRS that nonetheless required aggressive treatment.

T-ALL is a highly aggressive acute T-cell malignancy characterized by infiltration of the bone marrow and extramedullary tissues. Statistical data indicate that in 2015, approximately 876,000 individuals worldwide were affected by ALL, with 110,000 deaths attributed to the disease; among these cases, pediatric and adult patients with T-ALL accounted for approximately 15%–20%. An estimated 40%–50% of patients experience relapse within two years after first-line therapy, while other available treatment options are severely limited. There remains an urgent unmet medical need for the treatment of relapsed and refractory T-ALL.

In addition, Hengrui Medicine will also present the results of a multicenter, two-stage, Phase 2 clinical trial evaluating camrelizumab in combination with apatinib for the treatment of extensive-stage small cell lung cancer. Preliminary data from two pivotal studies of Genor Biopharma’s PD-1 monoclonal antibody, geptanolimab (GB226), will also be disclosed at this conference. These include efficacy and safety data from trials assessing GB226 for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) and unresectable recurrent or metastatic alveolar soft part sarcoma (ASPS). We look forward to these R&D programs yielding encouraging results that will advance clinical development and benefit patients sooner.

Jiangsu Hengrui Medicine Co., Ltd.

In China, camrelizumab, a novel PD-1 antibody developed by Hengrui Medicine, is a shining star. Previously, the drug had been successively approved in China for two indications: relapsed/refractory Hodgkin lymphoma and advanced hepatocellular carcinoma. Unsurprisingly, camrelizumab was also featured at this year’s AACR Annual Meeting, where results were presented from a multicenter, two-stage, Phase 2 clinical trial evaluating camrelizumab in combination with apatinib for the treatment of extensive-stage small cell lung cancer (SCLC).

The study enrolled 59 patients with previously platinum-resistant extensive-stage small cell lung cancer (SCLC), who were randomly assigned to three groups: apatinib 375 mg once daily, 5 days on/2 days off, and 7 days on/7 days off. Camrelizumab was administered at a dose of 200 mg every two weeks in all groups. The results showed that in the daily apatinib group, the objective response rate (ORR) was 34%, the median progression-free survival (PFS) was 3.6 months, and the median overall survival (OS) was 8.4 months. The incidence of grade 3 or higher treatment-related adverse events (AEs) was 72.9%, and the overall adverse reactions were manageable.

Apatinib is a small-molecule anti-angiogenic targeted drug that has been approved in China for the treatment of patients with advanced gastric cancer. Currently, a Phase 3 clinical study evaluating camrelizumab combined with apatinib as first-line therapy for advanced hepatocellular carcinoma is being conducted simultaneously across 123 centers in 14 countries and regions, including the United States, Russia, Belgium, Germany, France, Spain, Italy, Poland, and China.

References:

[1] AACR | Akeso Presents Preliminary Results from Phase Ib/II Study of Bispecific Antibody AK104 Combined with Chemotherapy as First-Line Treatment for Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma at AACR 2020. Retrieved May 27, 2019, from https://mp.weixin.qq.com/s?__biz=MzU3ODc1NDI4Mw==&mid=2247484012&idx=1&sn=187c3f2af433d6e59cc26683e5a34f92&chksm=fd71c1e8ca0648fea5f96a386061e90fb5672e96cc812a22c0264f19468c58a4e8f2f6348695&mpshare=1&scene=1&srcid=&sharer_sharetime=1587995752250&sharer_shareid=8d582ea620dd0fb882db91058f1d1cf4&exportkey=AYkH5KYxpm%2B0Lb0nMaRNDVk%3D&pass_ticket=PQfTb2oLwOZzzcf1qytKnwUz8G4n8ljgKWM4UDptu5fsNib1zMOjk2EvblctCJFF#rd

[2] 2020 AACR Annual Meeting | Latest Clinical Study Results of Hansoh Pharma’s Aumolertinib Announced. Retrieved May 27, 2019, from https://mp.weixin.qq.com/s?__biz=MzA5OTc5MjM0Mw==&mid=2649654658&idx=1&sn=2707f69784f8e8e4e8614dfb6b2075ce&chksm=88e6c13abf91482c9265553225f3d985ed87710e529b264018b0f42bf42a8c7b6e2ba3bc6d55&mpshare=1&scene=1&srcid=&sharer_sharetime=1587990274279&sharer_shareid=5b70c5c9594797f03fd6dffabbe8968a&exportkey=AVG3WIOHRcYVSvBIsZwF5VI%3D&pass_ticket=PQfTb2oLwOZzzcf1qytKnwUz8G4n8ljgKWM4UDptu5fsNib1zMOjk2EvblctCJFF#rd

[3] Gracell Biotechnologies presents first-in-human trial results of the universal TruUCAR™ GC027 therapy for relapsed or refractory acute T-cell lymphoblastic leukemia at the AACR Annual Meeting. Retrieved April 14, 2020 from https://www.gracellbio.com/cn/news-details.html?id=84

[4] Genor Biopharma Announces Presentation of Results from Two Clinical Trials of Geptanolimab at the 2020 AACR Annual Meeting. Retrieved April 14, 2020, from http://www.genorbio.com/M1.aspx?newid=1009