onatasertib (ATG-008) / Antengene, BMS - LARVOL DELTA

hCG Effects Are Related to the Day of Administration After Mating in Synchronous Estrus Induced Torki-Ghashghaei Sheep. (PubMed, Reprod Domest Anim) - "The results of the first experiment showed that the rate of multiple twinning, the number of lambs born, fecundity, prolificacy and progesterone concentration in ewes and ewe lambs receiving hCG on days 1.5 and two were significantly higher than those in the other groups (p < 0.05). Ewes and ewe lambs receiving hCG on days 1.5 and two had the best reproductive performance compared to the other groups. In conclusion, the application of hCG on 1.5 days after mating in Torki-Ghashghaei ewes and ewe lambs during the out-breeding season could be recommended for improving twinning rate, the number of lambs born and prolificacy rate."

Journal

Multicenter phase 1/2 study of onatasertib, a dual TORC1/2 inhibitor, combined with the PD-1 antibody toripalimab in advanced solid tumors. (PubMed, Signal Transduct Target Ther) - P1/2 | "In conclusion, the safety profile of onatasertib in combination with toripalimab was manageable and showed encouraging clinical activity in advanced solid tumors, particularly among cervical cancer patients, irrespective of PD-L1 expression. The recommended phase 2 dose for the combination was determined to be onatasertib 15 mg QD and toripalimab 240 mg Q3W."

IO biomarker • Journal • P1/2 data • Cervical Cancer • Oncology • Solid Tumor • PD-L1

A TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced cervical cancers with prior anti-PD-(L)1 therapy. (ASCO 2025) - P1/2 | "Additionally, 16 pts had prior abraxane treatment and 11 pts had prior bevacizumab therapy. Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in advanced CC pts with prior anti-PD-(L)1 therapy, regardless of PD-L1 expression. The expansion cohorts are ongoing."

Clinical • IO biomarker • Metastases • Cervical Cancer • Diabetes • Oncology • Solid Tumor

ATG-008 (mTORC1/2 Small Molecule Inhibitor) (PRNewswire) - P1/2 | N=60 | NCT04337463 | "This abstract reports data from patients with advanced cervical cancer who had previously received at least prior 1 line of anti-PD-(L)1 therapy and 1 line of platinum chemotherapy, regardless of the PD-L1 expression. As of November 25, 2024, 30 qualified patients were enrolled and received ATG-008 15 mg orally once a day (QD) in combination with toripalimab 240 mg, once every 21 days (Q3W). Among them, 14 and 16 patients had received 1 and at least 2 prior lines of systemic therapy, respectively. The median time since initial diagnosis was 37 months...Among 27 efficacy-evaluable patients, the combination regimen achieved an ORR of 22.2% and a DCR of 85.2%. The ORRs of PD-L1 positive and PD-L1 negative populations were 30% (3/10) and 33.3% (2/6), respectively."

P1/2 data • Cervical Cancer

Antengene to Present Latest Results From Two Clinical Studies at ASCO 2025 (PRNewswire) - "Antengene Corporation Limited...announced that it will release the latest clinical data of the CD73 small molecule inhibitor ATG-037 and the mTORC1/2 small molecule inhibitor ATG-008 in Poster Presentations at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting..."

Clinical data • Cervical Cancer

A phase 1/2 study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort. (ASCO 2024) - P1/2 | "Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in CC pts at the RP2D combination dose, regardless of PD-L1 expression. Enrolment in the expansion cohort for CPI-treated CC is ongoing, and updated data will be presented."

Clinical • IO biomarker • Metastases • P1/2 data • Cervical Cancer • Oncology • Solid Tumor

Antengene To Present One Oral and Four Abstracts at ASCO 2024 (PRNewswire) - P1/2 | N=60 | TORCH-2 (NCT04337463) | "Abstract: 5509:...31 checkpoint inhibitor (CPI)-naïve cervical cancer patients who previously had at least one systemic line of chemotherapy were enrolled in the TORCH-2 study as of Oct 20th 2023. ATG-008...combined with toripalimab (anti-PD-1 antibody) showed promising anti-tumor activity and acceptable tolerability in cervical cancer patients, achieving an overall response rate (ORR) of 53.3% and a disease control rate of 86.7%. In general, ATG-008 in combination with toripalimab are very well tolerated. The most common grade ≥ 3 treatment-related adverse events (TRAEs) included rash (12.9%), decreased lymphocyte count (9.7%), and decreased platelet count (6.5%). Encouraging response rates and disease stabilization were observed in patients, regardless of PD-L1 expression, with further data being collected in an ongoing expansion cohort for CPI-treated cervical cancer."

P1/2 data • Cervical Cancer

Antengene Announces One Oral and Three Poster Presentations at ASCO 2024 (PRNewswire) - "Antengene Corporation Limited...today announced the presentation of four abstracts (including one oral presentation and three poster presentations) at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting, taking place from May 31st to June 4th at the McCormick Place Convention Center in Chicago, IL, the United States."

P1 data • P1/2 data • Cervical Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Solid Tumor

GT0486, a novel mTORC1/2 dual inhibitor, exhibits synergistic antitumor efficacy in combination with BTK inhibitors (AACR 2024) - "Compared with other mTOR inhibitors (GDC-0349, AZD-2014, Rapamycin, GDC-0941, and CC-223), GT0486 exhibits the stronger inhibitory activity on human tumor cells, such as U87(glioma), PC-3(prostate cancer), MDA-MB-468(breast cancer) and Huh-7(liver cancer)...High synergistic effects were observed with GT0486 in combination with BTK inhibitors, including Acalabrutinib, Ibrutinib, Zanubrutinib and Orelabrutinib in the BTKi sensitive TMD8 cells...These results demonstrate that GT0486 is a promising dual mTOR1/2 inhibitor, which is currently undergoing clinical phase I study in China for the treatment of solid tumors. Strong synergistic effects observed with GT0486 in combination with BTKi in this study might open a way for a novel treatment strategy in clinical trials."

Clinical • Combination therapy • Brain Cancer • Breast Cancer • CNS Tumor • Gastrointestinal Cancer • Genito-urinary Cancer • Glioma • Hematological Malignancies • Liver Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor • EIF4EBP1

NEOS-223 is a small molecule kinase inhibitor which induces apoptosis in selected cancer models (AACR 2024) - "Most importantly, in vivo data showed that while administration of NEOS-223 alone decreased tumor growth, the addition of PI3K/Akt/mTOR inhibitor onatasertib significantly enhanced anticancer effect in a lung cancer model. In lung and pancreatic cancer models, inhibition of EGFR by the small molecule drug gefitinib strongly showed synergistic effect with NEOS-223 both in vitro and in vivo. This may be because EGFR potentially activates both the mitogen activated protein kinase (MAPK/ERK) and the PI3K/mTOR signaling cascades in different mutant cancer models. These studies reveal that NEOS-223 inhibits cell proliferation and induces apoptosis via suppressing the PI3K/Akt/mTOR pathway and further suggest that the combination of PI3K/Akt/mTOR and EGFR inhibitors and that NEOS-223 would be a strong potential chemotherapeutic strategy against lung and pancreatic cancers."

Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Antengene Announces Full Year 2023 Financial Results, Highlights Clinical Progress Across First-in-Class, Best-in-Class Pipeline (PRNewswire) - P1/2 | N=60 | TORCH-2 (NCT04337463) | "The Phase II 'TORCH-2' study is currently enrolling both checkpoint inhibitor (CPI)-naïve and CPI-pre-treated patients. Based on the latest data review as of March 14th, 2024, out of the 31 CPI-naïve patients who received treatment (30 had at least one tumor assessment), the objective response rate (ORR) was observed to be 53.3%, the disease control rate (DCR) was 86.7%. Among the 30 patients with prior CPI treatment (26 patients had at least one tumor assessment), the ORR was 23.1%, with a DCR of 84.6%. Next ATG-008 Milestone: Confirm registrational pathway in cervical cancer with health authorities."

P1/2 data • Oncology • Solid Tumor

Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov) - P1 | N=174 | Terminated | Sponsor: Celgene | Active, not recruiting ➔ Terminated; Replaced with another clinical trial.

Trial termination • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Antengene Presents Encouraging Clinical Data from Four Pipeline Programs at the 2023 R&D Day (PRNewswire) - P1/2 | N=60 | TORCH-2 (NCT04337463) | "Antengene Corporation Limited...is presenting encouraging clinical data of the Company's four key drugs in clinical development...at its 2023 R&D Day taking place today....ATG-008 (dual mTORC1/2 inhibitor): Clinical efficacy data have shown promising results from the Phase II TORCH-2 study evaluating ATG-008 in combination with toripalimab (anti-PD-1 antibody) for relapsed/metastatic cervical cancer patients. The trial enrolled 54 late-stage metastatic cervical cancer patients (30 CPI-naïve and 17 CPI-pre-treated patients with at least one tumor assessment). For the CPI-naïve patients, the objective response rate (ORR) is 53.3%, accompanied by a disease control rate (DCR) of 86.7% and a median progression-free survival (mPFS) of 8.41 months. For the CPI-pre-treated patients, the ORR, DCR, and mPFS stands at 29.4%, 82.4%, and 4.17 months respectively."

P2 data • Cervical Cancer

Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov) - P1 | N=174 | Active, not recruiting | Sponsor: Celgene | Phase classification: P1b ➔ P1 | Trial completion date: Oct 2023 ➔ Jan 2024 | Trial primary completion date: Oct 2023 ➔ Jan 2024

Phase classification • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Antengene to Host 2023 R&D Day and Discuss Key Data with KOLs (PRNewswire) - "Antengene Corporation Limited...announced that it will host its 2023 R&D Day on November 17, 2023, to update the medical and investor communities on the company's progress with its R&D programs. The session will feature three KOL sessions, and discussions about the data of Antengene's key drugs in clinical development, including ATG-031 (anti-CD24 monoclonal antibody), ATG-101 (PD-L1/4-1BB bispecific antibody), ATG-022 (Claudin 18.2 antibody-drug conjugate), ATG-037 (CD73 inhibitor), and ATG-008 (dual mTORC1/2 inhibitor); and updates on its proprietary R&D pipeline and upcoming development for 2024."

Clinical data • Oncology

Antengene Announces Interim Financial Results for 2023 with New Clinical Data Highlighting the Growing Value of Its Pipeline (PRNewswire) - "ATG-008 (mTORC1/2 inhibitor) unique, differentiated results in cervical cancer - The Phase II 'TORCH-2' study is currently enrolling both checkpoint inhibitor (CPI)-naïve and CPI-pre-treated cervical cancer patients....Updated clinical data will be presented in the Antengene Annual R&D Day in November."

Enrollment status • P1/2 data • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Novel agents in relapsed/refractory diffuse large B-cell lymphoma (ICML 2023) - "In recent years, numerous agents have been approved specifically for patients with DLBCL (RED) including tafasitamab, loncastuximab tesirine, polatuzumab vedotin, selinexor, rituximab, and pembrolizumab (for patients with Primary Mediastinal B-cell lymphoma)...Significant grade 3-4 toxicities were neutropenia and thrombocytopenia with 48.6% of patients requiring dose modifications, and 22.9% discontinuing treatment for toxicity.12 Ongoing and planned trials with loncastuximab include a phase III trial with rituximab, gemcitabine, and oxaliplatin (R-GemOx) (Tables 1 and 3)...Encouraging clinical activity, without unanticipated toxicities was observed when polatuzumab was combined with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) with an ORR of 89% (CR 61%).24 Combination of polatuzumab with lenalidomide and rituximab (R2) in 49 patients demonstrated an ORR of 35% (CR 29%), with median DOR, PFS, and OS of 8.1, 6.3, and 10.9 months, respectively...One notable..."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CARD11 • CD79B • CDKN1A • CRBN • CTLA4 • EZH2 • IKZF1 • IRAK4 • LYN • MALT1 • MCT1 • MYC • MYD88 • NF-κβ • PD-L1 • ROR1 • SIRPA • SYK • XPO1

Dual TORC1/TORC2 Inhibitor ATG-008 (CC-223) in HBV Positive Advanced Hepatocellular Carcinoma (HCC) Subjects (clinicaltrials.gov) - P2 | N=73 | Terminated | Sponsor: Antengene Therapeutics Limited | Trial completion date: Dec 2022 ➔ Aug 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Aug 2022; Based on the adjustment of clinical research and development strategy，sponsor decided to terminate the study

Metastases • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A phase 1/2 study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors. (ASCO 2023) - P1/2 | "Onatasertib in combination with tori is tolerable with encouraging response rate and disease stabilisation in pts with advanced solid tumors, especially in CC pts. Expansion enrolment for CC and NPC is ongoing. Clinical trial information: NCT04337463."

Clinical • IO biomarker • Metastases • P1/2 data • Cervical Cancer • Diabetes • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma (clinicaltrials.gov) - P1b | N=174 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Apr 2023 ➔ Jul 2023 | Trial primary completion date: Apr 2023 ➔ Jul 2023

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD20

Antengene To Present Latest Results from TORCH-2 Study of ATG-008 in Advanced Solid Tumors in Poster Discussion at ASCO 2023 (PRNewswire) - P1/2 | N=60 | TORCH-2 (NCT04337463) | "Antengene Corporation Limited...announced that the latest results from the Phase I/II TORCH-2 study will be presented as a poster at the 2023 American Society for Clinical Oncology Annual Meeting (ASCO 2023) taking place from June 2nd to 6th, 2023....The TORCH-2 study is a Phase I/II trial of the mTORC1/2 inhibitor ATG-008 plus the Anti-PD-1 monoclonal antibody toripalimab for the treatment of patients with advanced solid tumors. The combination treatment produced an objective response rate (ORR ) of 52.4% in the advanced cervical cancer cohort (including 75% in PD-L1 positive and 41.7% in PD-L1 negative patients), a disease control rate (DCR) of 90.5% and a median progression-free survival (mPFS) of 7.2 months."

P1/2 data • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer

Antengene to Release Latest Results from the TORCH-2 Trial of mTORC1/2 Inhibitor ATG-008 in Poster Discussion at 2023 ASCO (PRNewswire) - "Antengene Corporation Limited...announced that the results of the Phase I/II TORCH-2 study will be presented as a poster discussion during the American Society for Clinical Oncology Annual Meeting (ASCO 2023)....The TORCH-2 study is an open-label dose escalation and expansion study to evaluate ATG-008, an mTORC1/2 inhibitor, in combination with the anti-PD-L1 antibody, toripalimab, in patients with advanced solid tumors."

P1/2 data • Oncology • Solid Tumor

Result of an open-label phase 2 trial of dual TORC1/TORC2 inhibitor onatasertib (ATG-008) in HBV+ advanced hepatocellular carcinoma (HCC) subjects who have received at least one prior line of systemic therapy (TORCH) (AACR 2023) - P1/2, P2 | "Onatasertib (ATG-008) showed encouraging single agent antitumor activity in patients with HBV+ advanced HCC after at least 1 prior systemic therapy, notably in the 45 mg QD dose level, in which most patients had been previously exposed to anti-PD-L1/PD-1 therapy. The results indicates that onatasertib has potential efficacy in HBV+ HCC patients who failed prior CPI treatment. Further study may be warranted, particularly in HBV+ HCC patients who have failed prior anti-VEGFR and anti-PDL1/PD-1 therapy."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Oncology • Solid Tumor

Antengene Announces Five Presentations at the 2023 American Association for Cancer Research Meeting (PRNewswire) - P2 | N=73 | NCT03591965 | Sponsor: Antengene Therapeutics Limited | "Data from this study showed that 3 subjects achieved a partial response (PR), all in the 45 mg QD monotherapy cohort. A total of 18 patients were enrolled in this cohort that achieved an objective response rate (ORR) of 16.7%. Among them, 11 patients (61.1%) had received at least 2 prior lines of therapy and 15 patients had been exposed to an anti-PD-1/PD-L1 checkpoint inhibitor (CPI) (83.3%). The median progression-free survival (mPFS) was 3 months in the intend-to-treat (ITT) population and 5.3 months in the 45mg QD cohort."

P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

MATCH: A Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=7 | Terminated | Sponsor: Antengene Corporation | N=88 ➔ 7 | Trial completion date: Jun 2026 ➔ Feb 2023 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Feb 2023; Based on the adjustment of clinical research and development strategy，sponsor decided to terminate the study

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology