ascrinvacumab (GT90001) / Kintor Pharma, Pfizer - LARVOL DELTA

High affinity and potent anti-tumor efficacy of Nivo813, an anti-PD-1/ALK-1 bispecific antibody, in pre-clinical studies for solid tumors (AACR 2024) - P1/2 | "In the phase II clinical trial (NCT03893695) of combination therapy of ALK-1 (GT90001) and Nivolumab for the second line therapy in patients with metastatic hepatocellular carcinoma ("HCC") in Taiwan, among the 20 evaluable patients, the overall response rate is 40%, and the side effects were well tolerated and manageable. Nivo813, a dual-blocking anti-PD-1/ALK-1 bispecific antibody, shows improved binding potency to cell surface PD-1 and ALK-1 simultaneously, and displays dose-dependent anti-angiogenesis in vitro and great anti-tumor efficacy in vivo, supporting its clinical potentials for the treatment of human cancers."

Preclinical • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ACVRL1 • TGFB1

GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=5 | Active, not recruiting | Sponsor: Suzhou Kintor Pharmaceutical Inc, | Recruiting ➔ Active, not recruiting | N=105 ➔ 5 | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2023 ➔ Apr 2025

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Phase Ib/II Study of GT90001 Combined With KN046 in Solid Tumors (clinicaltrials.gov) - P1/2 | N=216 | Recruiting | Sponsor: Suzhou Kintor Pharmaceutical Inc, | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Apr 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • PD-L1

Combination of GT90001 and Nivolumab in Patients With Metastatic Hepatocellular Carcinoma(HCC) (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Suzhou Kintor Pharmaceutical Inc, | Active, not recruiting ➔ Completed

Trial completion • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Kintor Pharma Announces Publication of Phase Ib/II Data from GT90001 and Nivolumab Combination Therapy for Advanced HCC in BMC Medicine (Kintor Pharma Press Release) - P1b/2 | N=20 | NCT03893695 | Sponsor: Suzhou Kintor Pharmaceutical Inc, | "Kintor Pharmaceutical Limited...announced that the results of the Phase Ib/II clinical trial of ALK-1 antibody GT90001 combined with PD-1 antibody nivolumab in the treatment of advanced hepatocellular carcinoma (HCC) were published online by the well-known journal BMC Medicine....The confirmed objective response rate (confirmed ORR) and disease control rate (DCR) were 30% (95% CI, 14.6%-51.9%) and 40% (95% CI, 21.9%-61.3%), respectively. The median duration of response was not calculated (95% CI, 7.39 months to not calculated). Median progression-free survival (PFS) was 2.81 months (95% CI, 1.71–9.33), with 6-month and 12-month PFS rates of 35% and 25%, respectively. Furthermore, the combination of GT90001 and nivolumab showed a remarkable long-tail effect, since 8 subjects were still alive as of 19 April 2023."

P1/2 data • Hepatocellular Cancer

Combination of GT90001 and nivolumab in patients with advanced hepatocellular carcinoma: a multicenter, single-arm, phase 1b/2 study. (PubMed, BMC Med) - P1/2 | "GT90001 plus nivolumab has a manageable safety profile and promising anti-tumor activity in patients with advanced HCC."

Journal • Metastases • P1 data • P1/2 data • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Combination of GT90001 and nivolumab in patients with advanced hepatocellular carcinoma: a multicenter, single-arm, phase 1b/2 study (BMC Med) - P1/2 | N=20 | NCT03893695 | Sponsor: Suzhou Kintor Pharmaceutical Inc, | "In phase 1b, no dose-limiting toxicities were observed, and GT90001 7.0 mg/kg was confirmed as the RP2D. Common grade 3/4 adverse events (AEs) were platelet count decreased (15%). No deaths due to AEs were reported. Confirmed ORR and disease control rate were 30% (95% CI, 14.6%-51.9%) and 40% (95% CI, 21.9%-61.3%), respectively. Median duration of response was not calculated (95% CI, 7.39 months to not calculated). Median progression-free survival (PFS) was 2.81 months (95% CI, 1.71–9.33), with 6-month and 12-month PFS rates of 35% and 25%, respectively."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology

GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: Suzhou Kintor Pharmaceutical Inc, | Active, not recruiting ➔ Recruiting

Combination therapy • Enrollment open • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor

Kintor Pharma Announces First Patient Dosing in Multi-Regional Global Phase II Clinical Trial of ALK-1 Antibody and Nivolumab Combination Therapy for the Treatment of Advanced Hepatocellular Carcinoma (PRNewswire) - "Kintor Pharmaceutical Limited...announced the first patient dosing in the United States of its multi-regional phase II clinical trial (NCT05178043) of ALK-1 antibody (GT90001) and Nivolumab (Opdivo) combination therapy for the treatment of advanced Hepatocellular Carcinoma (HCC) on 2 May 2022."

Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Kintor Pharma Announces 2021 Business Progress and Annual Results (PRNewswire) - "Expected Milestones: (i) Kintor Pharma expects to dose the first patient of ALK-1 antibody's phase II clinical trial combined with nivolumab for the second-line treatment for advanced HCC in the US in H1 2022; (ii) Kintor Pharma expects to dose the first patient of GT90008's phase I clinical trial in China in H2 2022."

Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2; N=105; Active, not recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,

Clinical • Combination therapy • New P2 trial • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor

A Phase Ib/II Study of GT90001 Combined With KN046 in Solid Tumors (clinicaltrials.gov) - P1/2; N=216; Recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MRI • PD-L1

Kintor Pharma Doses First Patient in Clinical Trial of ALK-1 in Combination with KN046 In Advanced or Refractory Solid Tumors (PRNewswire) - "Kintor Pharmaceutical Limited...announced today that the company has enrolled and dosed its first patient with advanced or refractory solid tumors in a clinical trial of ALK-1 antibody (GT90001) in combination with KN046 on November 2 in Taiwan, China. This study (NCT04984668) is a two-stage, multicenter, open-label, phase Ib/II clinical trial to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of ALK-1 antibody in combination with KN046 in patients with advanced or refractory solid tumors, including hepatocellular carcinoma (HCC), gastric carcinoma/gastroesophageal junction adenocarcinoma (GC/GEJ), urothelial carcinoma (UC) and esophageal square cell carcinoma (ESCC)."

Trial status • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Urothelial Cancer

Kintor Pharma Announces China NMPA Approves Clinical Trial of ALK-1 and Nivolumab Combination Therapy for the First-line Treatment of Advanced Hepatocellular Carcinoma (PRNewswire) - "Kintor Pharmaceutical Limited...announced today that the clinical trial of ALK-1 antibody (GT90001C) and Nivolumab (Opdivo®) combination therapy for the treatment of systemic therapy naïve patients with advanced hepatocellular carcinoma ('HCC') was approved by the National Medical Products Administration (the 'NMPA') of China on October 9, 2021."

New trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

[VIRTUAL] Safety and efficacy of combination of GT90001, an anti-activin receptor-like kinase-1 (ALK-1) antibody, and nivolumab in patients with metastatic hepatocellular carcinoma (HCC). (ASCO-GI 2021) - P1/2 | "This study aimed to assess the safety and efficacy of GT90001 in combination with nivolumab in patients with advanced HCC who had progressive disease after or were intolerant to first-line sorafenib or lenvatinib therapy (NCT03893695). The combination of GT90001 with nivolumab showed a manageable safety profile, and no new safety signals were identified. The promising preliminary antitumor activities show the potential of GT90001 combined with nivolumab as second-line treatment for advanced HCC."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ALK1

A Phase Ib/II Study of GT90001 Combined With KN046 in Solid Tumors (clinicaltrials.gov) - P1/2; N=216; Not yet recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,

New P1/2 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MRI • PD-L1

Combination of GT90001 and Nivolumab in Patients With Metastatic Hepatocellular Carcinoma(HCC) (clinicaltrials.gov) - P1/2; N=20; Active, not recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,; Trial completion date: Jun 2021 ➔ Jun 2022; Trial primary completion date: Jun 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TGFB1

PF-03446962 in Relapsed or Refractory Urothelial Cancer (clinicaltrials.gov) - P2; N=14; Completed; Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; N=45 ➔ 14

Clinical • Enrollment change • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • EGFR • FLT1 • HER-2 • IL6 • KIT • PTEN

Combination of GT90001 and Nivolumab in Patients With Metastatic Hepatocellular Carcinoma(HCC) (clinicaltrials.gov) - P1/2; N=20; Active, not recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,; Trial completion date: Sep 2020 ➔ Jun 2021; Trial primary completion date: Sep 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Kintor‘s GT90001 and Nivolumab Combination Therapy Obtains Approval of Phase II Clinical Trial from US FDA for the Second-Line Treatment of Advanced Hepatocellular Carcinoma (Kintor Pharma Press Release) - "Kintor Pharmaceutical Limited...announce that the investigational new drug ('IND') application of GT90001 for a multi-regional phase II clinical trial for combination treatment of GT90001 and Nivolumab (Opdivo®) for the second-line treatment of advanced hepatocellular carcinoma ('HCC') was approved by the Food and Drug Administration (the 'US FDA') on February 11, 2021."

IND • Hepatocellular Cancer • Liver Cancer • Oncology

Combination of GT90001 and Nivolumab in Patients With Metastatic Hepatocellular Carcinoma(HCC) (clinicaltrials.gov) - P1/2; N=20; Active, not recruiting; Sponsor: Suzhou Kintor Pharmaceutical Inc,; Recruiting ➔ Active, not recruiting; Trial primary completion date: May 2020 ➔ Sep 2020

Clinical • Enrollment closed • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • VEGFA

Stellar Results from Kintor's GT90001 and Opdivo Combo Therapy in the Second-line Treatment of Advanced Liver Cancer: ORR Reached up to 40% (PRNewswire) - P1/2, N=20; NCT03893695; Sponsor: Suzhou Kintor Pharmaceutical Inc; "The preliminary data of the ongoing Phase II Clinical Trial showed positive efficacy and safety results. The data collected in the Phase II Clinical Trial will be released at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI) to be held between January 15-17, 2021...From July 9, 2019 to September 30, 2020, among the 20 evaluable patients, eight patients (40.0%) were observed partial remission (PR). The side effects were well tolerated and manageable. The pharmacokinetic parameters of GT90001 and Nivolumab are similar to those of monotherapy."

P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Therapeutic potential of targeting Transforming growth factor beta in colorectal cancer: Rational and Progress. (PubMed, Curr Pharm Des) - "These studies will be critical to improving the efficacy and selectivity of current and future anticancer strategies targeting TGF-β."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase Ib study of regorafenib (rego) and PF-03446962 (PF) in patients with refractory metastatic colorectal cancer (mCRC) (REGAL) (ASCO 2016) - Publication-only; P1, N=11; NCT02116894; "Among the 11 patients treated, treatment related AE included HFS (n = 4), abdominal pain (n = 3), fatigue (n = 4), anorexia (n = 3), dehydration (n = 3), and infusion reaction (n = 3)...Median progression free survival and overall survival were 2.0 mo (0.92-9.5) and 7.2 mo (1.2-NA), respectively."

P1 data • Colorectal Cancer • Oncology

A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial). (PubMed, Cancer Chemother Pharmacol) - "The regimen of regorafenib and PF-03446962 was associated with unacceptable toxicity and did not demonstrate notable clinical activity in patients with refractory metastatic colorectal cancer."

Clinical • Journal • P1 data • Anorexia • Back Pain • CNS Disorders • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Pain • Psychiatry • Solid Tumor