Phase 1 Dose Escalation and Expansion to Evaluate AROG4-01 in Patients With Advanced Solid Tumors

NCT06652529 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: AROG4-01-01
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if drug AROG4-01 is safe in patients with solid tumors who have no available treatment alternative. Different doses will be tested in order to identify the most suitable one. Once it is identiffied, up to 20 patients will be treated with that dose, to check if thye get clinical benefit. Participants will: receive intravenous administrations of ARG4-01 twice weekly, and visit the clinic twice every week for checkups and tests.

Conditions

Solid Tumors (Phase 1); Mesothelioma; Colorectal Carcinoma; Ovarian Cancer; NSCLC (Advanced Non-small Cell Lung Cancer)

Keywords

Phase I; AROG4-01; mesothelioma; solid tumors; NSCLC; ovarian cancer; colorectal cancer; dose escalation

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of AROG4-01

  To evaluate the safety and tolerability of AROG4-01 in adult patients with advanced solid tumors, including determination of the main DLT associated to AROG4-01. To assess the MTD (RP2D) defined as the highest dose at which no more than one in six patients experience a AROG4-01-related DLT. DLTs will be evaluated after the first treatment cycle.

  12 months

Secondary Outcomes (3)

• To assess the preliminary antitumor activity of AROG4-01 monotherapy as measured by Overall Response Rate (ORR) according to standard criteria (RECIST 1.1 [18] or mRECIST v1.1

  24 months

• To characterize the PK of AROG4-01.

  24 months

• To characterize the PK of AROG4-01

  12 months

Study Arms (1)

Dose escalation

EXPERIMENTAL

Four dose levels will be tested. If there are no safety concerns, dose escalation may continue with up to two additional dose levels

Drug: AROG4-01

Interventions

AROG4-01 DRUG

AROG4-01 will be administered as IV infusions in biweekly dosing interval. The first dosing day will be Day 1, 28 days cycle.

Also known as: Dose level 2, Dose level 3, Dose level 4, Dose level 5, Dose level 6, dose level 1

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 18 years or older, with a diagnosis (histology or citology) of advanced (unresectable or metastatic) solid tumor for which there is no curative therapy, has progressed on SOC treatment or for whom SOC is no longer an option. In part B patients will be included in different cohorts according to the histology (mesothelioma vs. non-mesothelioma).
• Evaluable (part A) or measurable disease (part B) as per RECIST v1.1 (part A) or mRECIST v1.1. (part B). Progressive disease to the on or following the last line of antitumor treatment.
• ECOG performance status ≤ 2.
• Life expectancy ≥12 weeks.
• Hematology and clinical chemistry laboratory parameters within acceptable ranges.
• Adequate organ function as defined below:
• Hemoglobin ≥9 g/dL
• Neutrophil count ≥1.000x10/mcL
• Platelets ≥100.000/mcL
• Total bilirubin ≤1,5 x Upper Limit of Normal (ULN) (unless Gilbert's Disease)
• AST (SGOT)/ALT (SGPT) ≤ 2,5 x institutional ULN (or ≤ 5X ULN in the presence of liver metastases)
• Creatinine ≤1.5 mg/dL and creatinine CL ≥40 mL/min (calculated using the Cockcroft-Gault formula)
• Adequate coagulation profile as defined below:
• INR≤ 1,5
• aPTT ≤ 1,5 x ULN

You may not qualify if:

• Systemic anti-cancer therapy within 4 weeks prior to study admission.
• Radiation therapy within 4 weeks prior to study entry.
• Any major surgery within 4 weeks before first dose of study treatment No major surgery must be planned during the trial expected treatment. receiving study treatment. Participants with recent surgery with only local anesthesia may be included.
• Non-malignant systemic disease including cerebrovascular accident, myocardial infarction in the last 6 months, unstable angina pectoris, unstable cardiac arrhythmia, New York Heart Association (NYHA) Class III or IV heart failure, coagulation abnormalities and clinically significant pulmonary compromise, .
• Left ventricular ejection fraction below institutional normal limits.
• Patients with symptomatic central nervous system (CNS) primary tumor or metastases (including leptomeningeal carcinomatosis). Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the investigator.
• Breast feeding, pregnancy or not willing to adopt safe contraceptive measures by the patient or the patient's partner, to become pregnant during treatment or within 6 months after the end of treatment.
• Patients with active uncontrolled infection or known to be serologically positive for human immunodeficiency virus (HIV), hepatitis B (except HbsAc after vaccination) or hepatitis C infection.
• Any other diseases or medical condition that may interfere with the planned treatment, compliance, or place the patient at risk if participating in the study, at investigator criteria.

Sponsors & Collaborators

• Aromics Therapeutics: lead

Related Publications (4)

• Aubets E, J Felix A, Garavis M, Reyes L, Avino A, Eritja R, Ciudad CJ, Noe V. Detection of a G-Quadruplex as a Regulatory Element in Thymidylate synthase for Gene Silencing Using Polypurine Reverse Hoogsteen Hairpins. Int J Mol Sci. 2020 Jul 16;21(14):5028. doi: 10.3390/ijms21145028.

  PMID: 32708710 BACKGROUND

• 19- Phan, A. T., & Patel, D. J. (2005). "RNA tetraplexes, structures and functions." Biochemistry, 44(2), 639-649. doi:10.1021/bi048804m

  BACKGROUND

• Simon, J. S., et al. (2018). "Hairpin structures near G-quadruplexes can modulate G4 stability and drug binding." Nature Communications, 9, 4621. doi:10.1038/s41467-018-07055-8

  BACKGROUND

• Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res. 2015 Oct 15;43(18):8627-37. doi: 10.1093/nar/gkv862. Epub 2015 Sep 8.

  PMID: 26350216 BACKGROUND

Related Links

• Company website

MeSH Terms

Conditions

Mesothelioma; Colorectal Neoplasms; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Carme Plasencia, PhD

CONTACT

+34 670 594 309; carme.plasencia@aromics.es

Sonia Macia, MD, PhD

CONTACT

+34606432153; sonia.macia@aromics.es

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This clinical trial is divided into two parts: dose escalation (part A), and dose expansion (part B). In part A (dose escalation), patients will be treated with AROG4-01 at different doses, starting at 9 mg/m2. Escalation to next dose levels will occur following the Safety Review Committee meeting for the most recently completed cohort. The MTD decided as per part A (dose escalation) will be used for part B (dose expansion).

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 22, 2024
• Study Start: January 1, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 7, 2024

Record last verified: 2024-11