ART0380 MESILATE (alnodesertib) for Advanced or metastatic solid tumours

Inclusion criteria

• {"criterion_text":"- 1.\tDiscontinued all previous treatments for cancer for at least 21d or 5 half-lives, whichever is shorter, and recovered from the acute effects of therapy to CTCAE Grade ≤1. Palliative Rt completed 1 week prior to start of study treatment\n- 10.\tSpecific criteria for B1:•Advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein. •Have at least 1 measurable lesion assessable by RECIST v1.1• ECOG 0-1•Combination arms: pat. for which irinotecan is an appropriate treatment. Prior treatment with irino is permitted\n- 11.\tSpecific criteria for B5:• ATM negative (histologically confirmed unresectable adenocarcinoma of the colon or rectum •Patients must have a maximum of 2 prior chemotherapy regimens for the treatment of advanced CRC and have demonstrated progressive disease or intolerance to their last regimen.. .•Have at least 1 measurable lesion assessable by RECIST v1.1.\n- 12.\tSpecific criteria for Part B6 •Patients with ATM negativemetastatic or locally advanced PDAC or acinar cell carcinoma. •Patients have received a maximum of 1 prior chemotherapy regimen for the treatment of advanced disease and have demonstrated progressive disease or intolerance to this regimen OR have received neoadjuvant/adjuvant therapy with recurrence occurring <6 months following completion of this treatment. •Have at least 1 measurable lesion assessable by RECIST v1.1.\n- 2.\tIf known germline BRCA mutation or a cancer with a somatic BRCA mutation or which is HRD positive and for which there is an approved PARP inhibitor, participants should have received such treatment before participating in the study unless contra-indicated\n- 3.\tAt least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 Guidelines\n- 4.\tHave adequate organ function\n- 5.\tSufficient non-irradiated tumor tissue sample available for submission for analysis\n- 6.\tFemale patients of childbearing potential and male patients with female partners of childbearing potential are required to use highly effective contraception plus one barrier method during their participation in the study and for 7 months and 5 months respectively following last dose\n- 7.\tEstimated life expectancy of ≥12 weeks\n- 8.\tPerformance status of 0-1 on the ECOG scale\n- 9.\tSpecific criteria for A3:• Advanced or metastatic Ca for which irinotecan is an appropriate treatment. Prior irino. is permitted •For food effect cohort only: Patients must be able to eat a high-fat meal within a 30-minute period, as provided by the study site"}

Exclusion criteria

• {"criterion_text":"- Women who are pregnant, breast feeding, or who plan to become pregnant while in the study or within 7 months after the last administration of study treatment\n- Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment\n- Received a live vaccine within 30 days before the first dose of study treatment\n- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate\n- Recent major surgery within 4 weeks prior to entry into the study or minor surgery within 1 week of entry into the study\n- Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks before the first dose of study treatment.\n- Have a history of allergy or hypersensitivity to study drug components\n- Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment\n- Currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study\n- Exclusion criteria for A3/B1/B5/B6 in combination with irinotecan: •Patients who have symptoms or signs of clinically unacceptable deterioration of the primary disease at the time of screening. • Patients who are known to be homozygous for both UGT1A1 *6 and *28 (UGT1A1 7/7 genotype), or simultaneously heterozygous for both UGT1A1 *6 and *28. • Patients receiving inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment will be excluded •Part B5: Patients who have received fruquintinib or regorafenib or trifluridine/tipiracil.•Part A3 Fed-fasted cohort only: Patients receiving acid reducing agents within 1 week before the first dose of study treatment will be excluded •Part B6: Neuroendocrine (carcinoid, islet cell) or adenosquamous carcinoma pancreatic cancer.\n- Men who plan to father a child while in the study or within 5 months after the last administration of study treatment\n- Serious concomitant systemic disorder that would compromise the participants ability to adhere to the protocol including: one or more opportunistic HIV/AIDs-related infections within the past 12 months, hepatitis B virus, or hepatitis C virus; Documented active or chronic tuberculosis infection; have had or currently have a malignancy in addition to the one currently being treated that is not in remission\n- Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).\n- Have moderate or severe cardiovascular disease"}

Primary endpoints

• {"endpoint_text":"- Part A: Incidence of dose-limiting toxicities (DLTs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Parts B1/B3/B4: Incidence and severity of AEs (CTCAE v5.0)","definition_or_measurement_approach":"CTCAE v5.0"}
• {"endpoint_text":"- Part B2: Progression free survival (RECIST v1.1)","definition_or_measurement_approach":"RECIST v1.1"}
• {"endpoint_text":"- Part B5/B6: Objective Response Rate","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Parts A/B1/B3/B4/B5/B6: Duration of Response, Best Overall Response, Objective Response Rate, Progression Free Survival, Overall Survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B2 Incidence and severity of AEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- ART0380 Plasma concentration data.","definition_or_measurement_approach":""}
• {"endpoint_text":"- ART0380 renal clearance data","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part B2: Objective Response Rate, Duration of Response (based on RECIST v1.1).","definition_or_measurement_approach":"RECIST v1.1"}
• {"endpoint_text":"- Archival tumor or pre-dose tumor biopsy: Correlation of lesions in (or indicative of lesions in) DNA repair pathways","definition_or_measurement_approach":""}
• {"endpoint_text":"- Plasma concentration data • Single dose PK parameters of ART0380 administered in fasting and fed states","definition_or_measurement_approach":"Single-dose PK parameters in fasting and fed states (PK analysis)"}

Spain

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

512

Number Of Sites

32

Number Of Participants

125

France

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

516

Number Of Sites

7

Number Of Participants

15

Primary sponsor

Full Name

Artios Pharma Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Third parties

• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Novogene (UK) Company Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"Central Lab Services and processing","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"IMD Institut fuer Medizinische Diagnostik Berlin-Potsdam GbR","duties_or_roles":"Sample processing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Frontage Laboratories Inc. (alternate address)","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Medicover Integrated Clinical Services Sp. z o.o.","duties_or_roles":"Sample processing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}