Actuate 1801: Elraglusib (9-ING-41) is an investigational study drug give alone or in combination with other chemotherapies, for the potential treatment of patients who have not been previously treated for pancreatic cancer that has spread to other parts of the body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Actuate Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Apr 2021 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Actuate Therapeutics Inc.

External identifiers

EU CT number

2024-518409-16-00

EudraCT number

2018-003739-32

ClinicalTrials.gov

NCT03678883

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Efficacy, Therapy, Pharmacodynamic

To determine the 1-year survival rate of patients treated on the elraglusib schedule chosen from the run-in stage of the study compared to the control arm.

Secondary objectives 2

1. To determine the rate of disease control of the combination of Elraglusib and gemcitabine/nab-paclitaxel (GA) in patients with pancreatic cancer without prior systemic therapy for advanced disease.
2. To correlate disease control rate with tumor molecular profiles.

Conditions and MedDRA coding

Refractory Hematologic Malignancies or Solid Tumors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
2. Is aged ≥ 18 years
3. Has pathologically or cytologically confirmed metastatic pancreatic cancer AND is previously untreated with systemic agents in the recurrence/metastatic setting AND would be a candidate to receive gemcitabine/nab-paclitaxel as a first-line treatment
4. Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)
5. Has laboratory function within specified parameters (may be repeated): a. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL b. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN); bilirubin ≤ 1.5 x ULN c. Adequate renal function: serum creatinine ≤ ULN OR creatinine clearance ≥ 60 mL/min for patients with a serum creatinine >ULN (calculated by the Cockcroft and Gault formula)
6. Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1
7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug: • Focal radiation therapy – 7 days • Surgery with general anesthesia – 7 days • Surgery with local anesthesia – 3 days
8. May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment
9. Puede haber recibido previamente dosis citotóxicas de quimioterapia sistémica como parte de un tratamiento neoadyuvante y/o adyuvante si las últimas dosis se han administrado al menos 6 meses antes del reclutamiento del estudio
10. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use highly effective contraceptive methods (refer to section 4.1.1 for specific definitions of highly effective methods of contraception) for the duration of study participation and in the following 6 months after discontinuation of study treatment
11. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 6 months after discontinuation of study treatment and use appropriate methods of contraception
12. Must not be receiving any other investigational medicinal product

Exclusion criteria 12

1. Is pregnant or lactating
2. Is known to be hypersensitive to any of the components of Elraglusib or to the excipients used in its formulation
3. Has endocrine or acinar pancreatic carcinoma
4. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and/or infertility. Recovery is defined as ≤ Grade 2 severity per CTCAE, v5.0
5. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of study therapy, or uncontrolled cardiac arrhythmia
6. Has had a myocardial infarction within 12 weeks of the first dose of study therapy or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator
7. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
8. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is consideredmajor)
9. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation.
10. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.
11. Has a current active malignancy other than pancreatic cancer
12. Is considered to be a member of a vulnerable population (for example, prisoners).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1-year survival rate of patients treated on the Elraglusib schedule chosen from the run-in portion of the study compared to the control arm.

Secondary endpoints 8

1. Disease control rate (DCR), defined as: Stable disease for ≥16 weeks, confirmed complete response, or confirmed partial response.
2. Objective response rate (ORR), defined as the percent of patients with Complete Response (CR) or Partial Response (PR) according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) criteria relative to the efficacy population.
3. Duration of Response (DOR), defined as the time from documentation of tumor response to disease progression
4. Progression-Free Survival (PFS), defined as the time from study enrolment until objective tumor progression or death
5. OS, defined as the time from study entry to death from any cause
6. Time to Treatment Failure (TTF)
7. Adverse events will be monitored from the date of first administration of Elraglusib and ending 30 days after the final administration of Elraglusib using the Common Terminology Criteria for Adverse Events (CTCAE), v5.0
8. Correlation of disease control rate with tumor molecular profiles

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Actuate Therapeutics Limited

Sponsor organisation

Actuate Therapeutics Limited

Address

The Black Church, Saint Mary's Place North Saint Mary's Place North

City

Dublin 7

Postcode

D07 P4AX

Country

Ireland

Scientific contact point

Organisation

Actuate Therapeutics Limited

Contact name

Steven Reich

Public contact point

Organisation

Actuate Therapeutics Limited

Contact name

Steven Reich

Third parties 8

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 21 files

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

Application history

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