ibrilatazar (ABTL0812) / Ability Pharma, SciClone - LARVOL DELTA

ENDOLUNG trial, part II. A phase II study of the Akt/mTOR inhibitor and autophagy inducer ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with squamous non-small cell lung cancer. (PubMed, Lung Cancer) - "Ibrilatazar combined with paclitaxel and carboplatin shows promising efficacy and safety in sq-NSCLC, warranting further clinical development."

Journal • P2 data • Hematological Disorders • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ENDOLUNG trial, part II. A phase II study of the Akt/mTOR inhibitor and autophagy inducer ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with squamous non-small cell lung cancer (Lung Cancer) - P1/2 | N=103 | ENDOLUNG (NCT03366480) | Sponsor: Ability Pharmaceuticals SL | "40 patients were enrolled constituting the intention-to-treat (ITT) population (90 % male, median age 66, ECOG 0–1). The efficacy analysis (FA) subset included 25 patients, excluding 15 patients without a measurement of the primary variable. For ITT and FA populations, the ORR was 32.5 % (95 % Confidence Interval (CI) 21.3–50.1) vs 52.0 % (95 % CI 34.2–65.9), the disease control rate (DCR) was 52.5 % (95 % CI: 36.1–68.5) vs 84.0 % (95 % CI: 63.9–95.5), the PFS was identical (6.2 months; 95 % CI: 4.4–8.8) and the OS was 18.4 months (95 % CI: 9.5-NC) and 22.5 months (95 % CI: 10.4-NC), respectively."

P2 data • Lung Non-Small Cell Squamous Cancer

A Study of ABTL0812 in Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=60 | Suspended | Sponsor: Ability Pharmaceuticals SL | Trial completion date: Apr 2024 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

ENDOLUNG trial. A phase 1/2 study of the Akt/mTOR inhibitor and autophagy inducer Ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with advanced/recurrent endometrial cancer (BMC Cancer) - P1/2 | N=103 | ENDOLUNG (NCT03366480) | Sponsor: Ability Pharmaceuticals SL | "During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid....The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND)....This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC."

P1/2 data • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

ENDOLUNG trial. A phase 1/2 study of the Akt/mTOR inhibitor and autophagy inducer Ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with advanced/recurrent endometrial cancer. (PubMed, BMC Cancer) - P1/2 | "This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials."

Combination therapy • Journal • Metastases • P1/2 data • Endometrial Cancer • Febrile Neutropenia • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

PanC-ASAP: ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P1/2 | N=150 | Completed | Sponsor: Ability Pharmaceuticals SL | Trial completion date: Sep 2028 ➔ Jan 2024 | Trial primary completion date: Dec 2024 ➔ Jan 2024 | Recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

AbilityPharma Announces € 7 Million Financing Round to Advance Development of its Clinical Phase 2b Autophagy Inducer ABTL0812 in Metastatic Pancreatic Cancer (PRNewswire) - "The Catalan biopharmaceutical company Ability Pharmaceuticals, SA...announces a €7M investment from a European-Canadian syndicate of life sciences investors, including CTI Life Sciences Fund, Inveready, the EIC Fund, Fitalent and CDTI Innvierte. The funding will allow the Company to fully finance its phase 2b clinical study of antitumor compound ABTL0812 in patients with pancreatic cancer...AbilityPharma is completing a Phase 2b clinical trial with ABTL0812 in metastatic pancreatic cancer (all 140 patients recruited) with the aim of demonstrating greater efficacy than standard treatment FOLFIRINOX...Efficacy results are expected by year-end....Significant superior efficacy results will allow AbilityPharma to obtain financing for final development of ABTL0812 or to license it to a multinational pharmaceutical or biotechnology company, with the goal of making ABTL0812 available to pancreatic cancer patients in 2028."

Financing • Launch • P2b data • Pancreatic Cancer

PanC-ASAP: ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Ability Pharmaceuticals SL | Phase classification: P2 ➔ P1/2

Phase classification • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Phase 2 clinical trial of the proautophagic drug ABTL0812 combined with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung carcinoma. (ASCO 2023) - P1/2 | "The combination of ABTL0812 with paclitaxel and carboplatin shows survival outcomes that compare favorably with historical controls in squamous-NSCLC with an acceptable safety profile. PK analysis is compatible with drug activity, and pharmacodynamic analysis shows drug engagement. Clinical trial information: NCT03366480."

Clinical • Metastases • P2 data • Anemia • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • TRIB3

PanC-ASAP: ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Ability Pharmaceuticals SL | Trial completion date: Mar 2025 ➔ Sep 2028 | Trial primary completion date: Mar 2023 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study of ABTL0812 in Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=60 | Suspended | Sponsor: Ability Pharmaceuticals SL | N=110 ➔ 60 | Trial completion date: Mar 2023 ➔ Apr 2024 | Not yet recruiting ➔ Suspended | Trial primary completion date: Mar 2022 ➔ Apr 2023

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial suspension • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models. (PubMed, Front Oncol) - "Finally, we investigated the combination of ABTL0812 with the standard of care treatments for GBM radiotherapy and temozolomide in an orthotopic model, detecting that ABTL0812 potentiates the efficacy of both treatments and that the strongest effect is obtained with the triple combination of ABTL0812+radiotherapy+temozolomide. Overall, the present study demonstrated the anticancer efficacy of ABTL0812 as single agent and in combination with the GBM standard of care treatments in models of glioblastoma and supports the clinical investigation of ABTL0812 as a potential novel therapy for this aggressive brain tumor type."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Oral Cancer • Solid Tumor • TRIB3

Anticancer Effects of ABTL0812, a Clinical Stage Drug Inducer of Autophagy-mediated Cancer Cell Death, in Glioblastoma Models (Clin Cancer Res) - "ABTL0812 anticancer efficacy was studied in vivo using subcutaneous and orthotopic intra-brain xenograft tumor models. We demonstrated that ABTL0812 impairs tumor growth and increases disease-free survival and overall survival of mice....The present study demonstrated the anticancer efficacy of ABTL0812 as single agent and in combination with the GBM standard of care treatments in models of glioblastoma."

Preclinical

ABTL0812 enhances antitumor effect of paclitaxel and reverts chemoresistance in triple-negative breast cancer models. (PubMed, Cancer Commun (Lond)) - No abstract available

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

[VIRTUAL] Phase II of ABTL0812, a pro-autophagic drug, in combination with paclitaxel and carboplatin (P/C) as first-line treatment in advanced/recurrent endometrial cancer (ESMO 2020) - P1/2 | "Funding: Ability Pharmaceuticals SL. Clinical trial identification: EudraCT: 2016-001352-21."

Clinical • Combination therapy • P2 data • Endometrial Cancer • Gynecologic Cancers • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • TRIB3

Phase 1 of ABTL0812, a proautophagic drug, in combination with paclitaxel and carboplatin at first-line in advanced endometrial cancer and squamous cell lung carcinoma. (ASCO 2019) - P1/2; "The combination of ABTL0812+P/C was safe and tolerated, efficacy signals were observed, and biomarker modulation confirmed drug activity. The triple combination is currently being evaluated in both indications in a Phase 2 study. Clinical trial information: NCT03366480"

Clinical • Combination therapy • P1 data

[VIRTUAL] Phase 2 of Pro-Autophagic Drug ABTL0812 in Combination With First-Line Paclitaxel and Carboplatin in IIIb/IV Squamous NSCLC (IASLC-WCLC 2020) - "There is a trend to increased efficacy with no increased toxicity and an acceptable safety and tolerability profile. PK and PD profiles indicate sustained target modulation."

Clinical • Combination therapy • P2 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TRIB3

ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Ability Pharmaceuticals SL; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

LoA Update: Ability Pharmaceuticals’ potential to drive Phase I/IIa endometrial cancer drug to next development stage increases to 47% (Clinical Trials Arena) - P1/2, N=103; Endolung (NCT03366480); Sponsor: Ability Pharmaceuticals SL; "Ability Pharmaceuticals’ targeted drug ABTL-0812 improved its chances to transition to the next development stage by 14 points after a Phase I/IIa trial was completed, as of 29 June....In this update, 34 evaluable patients advanced or recurrent endometrial carcinoma, except carcinosarcoma and leiomyosarcoma, were treated with ABTL-0812 with carboplatin/paclitaxel every three weeks as a frontline therapy, followed by ABT-0812 as a maintenance therapy. In this group, the overall response rate (ORR) was 66%, and the duration of response was 7.8 months (Leary et al, Annals of Oncology, volume 31, supplement 4, S639-S640)."

P1/2 data • Endometrial Cancer • Gynecologic Cancers • Oncology

Endolung: A Study to Assess the Efficacy and Safety of ABTL0812 (clinicaltrials.gov) - P1/2; N=103; Completed; Sponsor: Ability Pharmaceuticals SL; Recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Endometrial Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] ABTL0812, a Phase 2 clinical stage pro-autophagy anticancer drug exhibits immunomodulatory effects that modify tumor microenvironment in pancreatic cancer models (AACR 2021) - "Overall, these multiple actions could potentially help to transform “cold” non-immunogenic tumors into “hot” immunogenic tumors and contribute to elicit anticancer immunosurveillance. These novel findings support further investigation of ABTL0812 in combination with immunotherapy to treat cancer"

Biomarker • Clinical • IO biomarker • P2 data • Preclinical • Tumor microenvironment • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CALR • CD4 • CD8 • CXCL5 • GLI2 • HMGB1 • IL10 • IL1B • KRAS • STAT3 • TNFA • TRIB3

A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours. (PubMed, Eur J Cancer) - P1 | "ABTL0812 is safe and has an acceptable tolerability profile, allowing a long-term oral dosing. RP2D of 1300 mg three times a day was determined according to PK/PD modelling, and preliminary antitumour efficacy was observed."

Clinical • Journal • Gastrointestinal Disorder • Oncology • Solid Tumor

ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P2; N=150; Not yet recruiting; Sponsor: Ability Pharmaceuticals SL; Trial completion date: Dec 2022 ➔ Mar 2025; Trial primary completion date: Sep 2022 ➔ Mar 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (clinicaltrials.gov) - P2; N=150; Not yet recruiting; Sponsor: Ability Pharmaceuticals SL; Initiation date: Dec 2020 ➔ Mar 2021

Clinical • Combination therapy • Trial initiation date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis. (PubMed, Cell Death Dis) - "Remarkably, ABTL0812 potentiated the antitumour activity of chemotherapies and differentiating agents such as irinotecan and 13-cis-retinoic acid. In conclusion, ABTL0812 distinctive mechanism of action makes it standout to be used alone or in combination in high-risk neuroblastoma patients."

Journal • Neuroblastoma • Oncology • Solid Tumor