sitneprotafib (JAB-3312) / Jacobio Pharma, Allist - LARVOL DELTA

JAB-3312 Based Combination Therapy in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=58 | Completed | Sponsor: Allist Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=200 ➔ 58

Enrollment change • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of JAB-3312 in Adult Patients with Advanced Solid Tumors in China (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | Trial completion date: Dec 2023 ➔ Apr 2026 | Trial primary completion date: Dec 2023 ➔ Apr 2025

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

JAB-21822-1006: Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients with Advanced Solid Tumors Harboring KRAS P.G12C Mutation (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Allist Pharmaceuticals, Inc. | N=124 ➔ 240

Enrollment change • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Jacobio Presents Pre-clinical Data of SHP2 plus KRAS G12C (Jacobio Press Release) - "Jacobio Pharma...presented the pre-clinical data of SHP2 inhibitor JAB-3312 in combo with KRAS G12C inhibitor glecirasib as form of poster at the Fifth RAS Initiative Symposium 2024. The data showed that glecirasib and JAB-3312 demonstrate potent anti-tumor effect both in vitro and in vivo, and JAB-3312 enhances the anti-tumor effect of glecirasib. Representative patients cases were also included in the poster."

Preclinical • Oncology

Jakos (01167.HK): Received RMB 173 million including down payment from exclusive external licensing agreement with Ellis [Google translation] (Yahoo Finance) - "Jakosi...announced that on August 30, its indirect non-wholly owned subsidiary Jakosi’s new drug research and development project was announced by Ellison on the KRAS G12C inhibitor Glecirasib (JAB-21822) and the SHP2 allosteric inhibitor JAB-3312. For the external licensing agreement entered into, a payment of RMB 173 million (the same below) has been received, including a down payment of RMB 150 million and partial compensation for research and development expenses and other payments."

Financing • Oncology

Efficacy of glecirasib in combination with JAB-3312 as a front-line treatment for patients with KRAS p.G12C mutated NSCLC with PD-L1 expression levels or co-mutations (ESMO 2024) - P1/2 | "Glecirasib plus JAB-3312 demonstrated a favorable ORR as a front-line treatment in KRAS p.G12C mutated NSCLC, regardless of PD-L1 expression. Co-mutations in SMARC family members may predict poor prognosis in this study population. More data will be presented at the incoming meeting."

Biomarker • Clinical • Combination therapy • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1 • TP53

JAB-21822 3002: JAB-21822 Combined With JAB-3312 Compared SOC in the First Line for Treatment of Advanced Non-small Cell Lung Cancer With KRAS p.G12C Mutation (clinicaltrials.gov) - P3 | N=392 | Recruiting | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jacobio Out-licensed KRAS G12C Inhibitor Glecirasib and SHP2 Inhibitor JAB-3312 to Allist in China (PRNewswire) - "Jacobio Pharma...announced that it has granted the China rights (including mainland China, Hong Kong, Macau, and Taiwan) of KRAS G12C inhibitor glecirasib and SHP2 inhibitor JAB-3312 to Shanghai Allist Pharmaceuticals Co., Ltd (688578.SH). According to the terms of the agreement, Jacobio shall receive around RMB200 million in the near term, which includes an upfront payment of RMB150 million, and around RMB50 million of compensation for research and development expenses and other payments....Jacobio is also entitled to receive tiered double-digit royalty payments on net sales of glecirasib and JAB-3312 from Allist, among which the royalty payments on net sales of JAB-3312 is up to 20%."

Commercial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

After being "returned" by AbbVie, Jacobs terminated the development of a SHP2-targeted drug [Google translation] (Sina Corp) - "...CASI Pharmaceuticals mentioned that the clinical development of the SHP2 allosteric inhibitor JAB-3068 has been terminated....In February of this year, JAB-3312 and the KRAS G12C inhibitor JAB-21822 were approved for Phase III clinical trials in China, becoming the world's first SHP2 inhibitor to enter Phase III registration clinical studies. Relevant clinical data are expected to be announced in the second half of this year."

Discontinued • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment. (PubMed, J Med Chem) - "JAB-3312 was well-tolerated in animal models, and a close correlation was observed between the plasma concentration of JAB-3312 and the p-ERK inhibition in tumors. Currently, JAB-3312 is undergoing clinical trials as a potential anticancer agent."

Journal • Oncology • PD-1

Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors. (ASCO 2024) - P1/2 | "Glecirasib plus JAB-3312 has a manageable safety profile and a promising ORR and PFS as a front-line treatment for patients with KRAS p.G12C NSCLC. This combination will be further evaluated in a randomized phase III trial in NSCLC."

Clinical • Anemia • Colorectal Cancer • Dyslipidemia • Gastrointestinal Cancer • Hematological Disorders • Hypertriglyceridemia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Jacobio Pharma Presents SHP2 Plus KRAS G12C Data at ASCO (PRNewswire) - P1/2a | N=124 | NCT05288205 | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | "About 102 frontline NSCLC patients have been enrolled in 7 dose groups. The confirmed objective response rate (cORR) was 64.7% (66/102), the disease control rate (DCR) was 93.1% (95/102), and the median progression-free survival (mPFS) was 12.2 months, respectively. This trial explored a total of 7 different dose cohorts, and the optimal dose group was glecirasib at 800mg daily combined with JAB-3312 at 2mg daily one week on and one week off. The cORR of the optimal dose group was 77.4% (18/31), and 54.8% (17/31) of patients achieved a deep response with tumors shrinking by more than 50%....The new drug application (NDA) of glecirasib monotherapy for the second-line NSCLC with KRAS G12C mutation was granted Priority Review designation by China CDE on May 21, 2024."

P2a data • Priority review • Non Small Cell Lung Cancer

JAB-21822 3002: JAB-21822 Combined With JAB-3312 Compared SOC in the First Line for Treatment of Advanced Non-small Cell Lung Cancer With KRAS p.G12C Mutation (clinicaltrials.gov) - P3 | N=392 | Not yet recruiting | Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Metastases • New P3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jacobio Pharma Announces 2023 Annual Results (PRNewswire) - "SHP2 inhibitor JAB-3312: The Phase III pivotal trial of JAB-3312 in combination with glecirasib to treat 1L NSCLC patients has been approved by CDE, and this study in China is expected to initiated in Q3 2024. JAB-3312 is the very first SHP2 inhibitor entering a phase III registrational trial worldwide; Long term safety and efficacy data have submitted to the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting."

New P3 trial • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jacobio Announces China CDE Clearance for Phase III Clinical Trial of SHP2 Inhibitor Plus KRAS G12C Inhibitor (PRNewswire) - "Jacobio Pharma...today announced it received approval of registrational phase III clinical trial of the combination therapy between its novel KRAS G12C inhibitor glecirasib and novel SHP2 inhibitor JAB-3312....This approved study in China is a randomized active controlled phase III trial design to evaluate the efficacy and safety of JAB-3312 in combination with glecirasib for first-line non-small cell lung cancer patients with KRAS G12C mutations. The control arm is the current standard treatment for first-line non-small cell lung cancer, which is the combination therapy of PD-1 antibody and chemotherapy."

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study to investigate JAB-3312 Combination Therapies in Adult Patients with Advanced Solid Tumors (clinicaltrialsregister.eu) - P2 | N=20 | Ongoing | Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Combination therapy • Metastases • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Glecirasib (KRAS G12C inhibitor) in combination with JAB-3312 (SHP2 inhibitor) in patients with KRAS p.G12C mutated solid tumors (ESMO 2023) - P1/2 | "Conclusions Glecirasib plus JAB-3312 was well tolerated with promising efficacy in KRAS p.G12C NSCLC. Currently, dose expansion is underway to further evaluate efficacy and safety."

Clinical • Combination therapy • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Jacobio Pharma Presents Clinical Results of Glecirasib in Combination with JAB-3312 at ESMO (PRNewswire) - P1/2 | N=124 | NCT05288205 | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | "Jacobio Pharma...announce that the clinical data of glecirasib in combination with JAB-3312 was published in the form of a proffered paper presentation at the 2023 European Society for Medical Oncology Congress (ESMO 2023)....Among the 129 NSCLC (non-small cell lung cancer) patients involved in the trial, 107 patients had undergone at least one tumor assessment using RECIST1.1 criteria, and 58 of them were first-line therapy patients (spread across the seven dose groups), with an ORR of 65.5% (38/58) and a DCR of 100%. The ORR was 86.7% (13/15) in the dose group of 800 mg glecirasib in combination with 2 mg JAB-3312."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jacobio Pharma Announces 2023 Interim Results (PRNewswire) - "Development of core clinical stage products:...SHP2 inhibitors: JAB-3312 - In combination with KRAS G12C inhibitor: JAB-3312 is currently enrolled in the Phase I/IIa clinical trial with glecirasib in China, with over 100 patients enrolled. The Phase IIa dose expansion trial of JAB-3312 in combination with sotorasib is ongoing in Europe and the U.S. The preliminary clinical results will be presented in the form of a Proffered Paper presentation at the 2023 European Society for Medical Oncology (ESMO) Congress in October 2023."

P1/2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

Jacobio Pharma to Present Data of Glecirasib in Combination with JAB-3312 at the 2023 ESMO Conference (PRNewswire) - "Jacobio Pharma...is pleased to announce today that the company will present its clinical results in the form of Proffered Paper presentation at the 2023 European Society for Medical Oncology (ESMO) Congress."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thoracic Cancer

JAB-3312 Based Combination Therapy in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | Trial completion date: Jun 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Jan 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Jacobio Pharma Announces 2022 Annual Results (PRNewswire) - "Data publication plan in 2023: (i) ASCO 2023 (submitted): The clinical data of Glecirasib in combination with Cetuximab in patients with CRC; (ii) ESMO 2023 (planed): The clinical data of SHP2 inhibitor JAB-3312 in combination with Glecirasib; (iii) 2023 H2-2024 H1 (planed): Glecirasib monotherapy in PDAC and other solid tumors - expect to read out preliminary data for this study."

Clinical data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Investigation of KRAS G12C inhibitor JAB-21822 as a single agent and in combination with SHP2 inhibitor JAB-3312 in preclinical cancer models (ESMO Asia 2022) - "Background While the currently available KRASG12C-selective inhibitors including Sotorasib have shown promising efficacy, acquired resistance eventually occurred in most cancer patients following treatment. Conclusions JAB-21822 is a promising KRASG12C-targeting drug and, when combined with JAB-3312, can overcome adaptive resistance to KRASG12C inhibition. These preclinical data have provided rationale for our clinical trial featuring the two drugs combination in treating KRASG12C inhibitor-resistant cancer patients."

Combination therapy • Preclinical • Oncology • KRAS

Jacobio's Preclinical Results of KRAS G12C Inhibitor in Combination with SHP2 Inhibitor Will be Presented at the ESMO Asia Congress 2022 (PRNewswire) - "Jacobio Pharma...will present the results of KRAS G12C inhibitor JAB-21822 as a single agent or in combination with SHP2 inhibitor JAB-3312 in preclinical cancer models in a poster session during the 2022 European Society of Medical Oncology ASIA (ESMO ASIA) Congress from December 2, 2022 to December 4, 2022. The results of preclinical study showed that JAB-21822 in combination with JAB-3312 could synergistically inhibit tumor growth in multiple KRAS G12C inhibitor-resistant models, suggesting that the combination of JAB-21822 and JAB-3312 may overcome adaptive resistance to KRAS G12C inhibitor in cancer patients."

Preclinical • Oncology

Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation (clinicaltrials.gov) - P1/2 | N=124 | Recruiting | Sponsor: Jacobio Pharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting | N=72 ➔ 124

Combination therapy • Enrollment change • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS