A clinical study to assess the safety and efficacy of oral ART0380 as a single agent or in combination in solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Artios Pharma Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2025 → ongoing

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Artios Pharma Limited - UK

External identifiers

EU CT number

2024-511534-12-00

EudraCT number

2021-003472-14

ClinicalTrials.gov

NCT04657068

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Dose response, Pharmacodynamic

1. Part A: Safety and tolerability of ART0380 given orally in patients with advanced or metastatic solid tumors and to determine the maximum tolerated dose (MTD) and/or recommended Phase II doses/schedules (RP2Ds) of ART0380 as monotherapy, in combination with gemcitabine or in combination with irinotecan.
2. Parts B1/B3/B4: To further assess the safety and tolerability of ART0380 given orally as monotherapy, and/or ART0380 in combination with irinotecan RP2Ds.
3. Part B2: To compare the efficacy of ART0380 in combination with gemcitabine versus gemcitabine alone in patients with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma that is resistant to platinum (PFI <6 months).
4. Parts B5/B6: To assess the efficacy of ART0380 in combination with irinotecan in patients with:
• ATM negative CRC that has previously been treated with a maximum of 2 prior chemotherapy regimens for advanced CRC (Part B5)
• ATM negative metastatic or locally advanced PDAC or acinar cell carcinoma that has previously been treated with a maximum of 1 prior chemotherapy regimen for advanced disease (Part B6).

Secondary objectives 7

1. Parts B1/B3/B4/B5/B6: To assess preliminary signs of efficacy of ART0380 given orally as monotherapy, and/or ART0380 in combination with irinotecan RP2Ds. Part A: To assess preliminary signs of efficacy of ART0380 given orally as monotherapy, in combination with gemcitabine or in combination with irinotecan.
2. Further assess thesafety and tolerability of ART0380 at the RP2D with gemcitabine vs. gemcitabinealone (Part B2) and of ART0380 at the RP2D in combination with irinotecan.
3. Determine ART0380 PK following single and multiple dosing in combination with gemcitabine (Part A2), in combination with irinotecan (Part A3), in advanced or metastatic solid tumors with alterations in the ATM gene likely to predict for loss of ATM protein (Part B1), in biologically-selected endometrial cancer (Part B3), solid tumors (Part B4), in metastatic CRC (Part B5) or in metastatic or locally advanced pancreatic ductal adenocarcinoma (PDAC) or acinar cell carcinoma (Part B6)
4. Part B2: Assess signs of efficacy for ART0380 with gem. vs gem. alone in pat. with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma Plt resistant
5. Assess markers in tumor samples that may predict ART0380 activity
6. Determine irino PK and its metabolite SN38 following single and multiple dosing of ART0380 in combination with irino.
7. To explore the effects of food on the PK of ART0380.

Conditions and MedDRA coding

Advanced or Metastatic Solid Tumours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Discontinued 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
2. 2. If 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
3. 3. At 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
4. 4. Have adequate organ function
5. 5. Sufficient non-irradiated tumor tissue sample available for submission for analysis
6. 6. Female 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
7. 7. Estimated life expectancy of ≥12 weeks
8. 8. Performance status of 0-1 on the ECOG scale
9. 9. Specific 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
10. 10. Specific 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
11. 11. Specific 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.
12. 12. Specific 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.

Exclusion criteria 14

1. 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
2. Have a history of allergy or hypersensitivity to study drug components
3. Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
4. 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
5. 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.
6. Men who plan to father a child while in the study or within 5 months after the last administration of study treatment
7. 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
8. Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
9. Have moderate or severe cardiovascular disease
10. Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
11. Received a live vaccine within 30 days before the first dose of study treatment
12. 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
13. Recent major surgery within 4 weeks prior to entry into the study or minor surgery within 1 week of entry into the study
14. Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks before the first dose of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part A: Incidence of dose-limiting toxicities (DLTs)
2. Parts B1/B3/B4: Incidence and severity of AEs (CTCAE v5.0)
3. Part B2: Progression free survival (RECIST v1.1)
4. Part B5/B6: Objective Response Rate

Secondary endpoints 7

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Artios Pharma Limited

Sponsor organisation

Artios Pharma Limited

Address

Babraham Hall, Babraham Research Campus Babraham Research Campus

City

Cambridge

Postcode

CB22 3AT

Country

United Kingdom

Scientific contact point

Organisation

Artios Pharma Limited

Contact name

Chief Medical Officer

Public contact point

Organisation

Artios Pharma Limited

Contact name

Chief Medical Officer

Third parties 10

Locations

2 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications