A Study to Assess an ATX Inhibitor (IOA-289) in Patients With Metastatic Pancreatic Cancer

NCT05586516 | Completed Phase 1 DMC

• 1 other identifier: IOA-289-102
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 3

Brief Summary

The objective of study IOA-289-102 is to evaluate the safety and tolerability of escalating doses of IOA-289 in patients with metastatic pancreatic cancer in combination with standard chemotherapy consisting of gemcitabine and nab-paclitaxel. Blood and tumour samples for PK and PD will be collected and assessments for determination of any clinical efficacy will be completed.

Conditions

Metastatic Pancreatic Cancer

Keywords

Metastatic; Pancreatic; Cancer; Autotaxin; ATX; Lysophosphatidic acid; LPA; Fibrosis; Immune

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events [Safety and Tolerability]

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Adverse event assessment will be assessed by CTCAE v5.0, through study completion, an average of 1 year.

Secondary Outcomes (15)

• Cmax

  at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.

• Cmin

  at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.

• t½

  at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.

• tmax

  at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.

• AUC0-t

  at Cycle 0 Day 1 (pre-dose and 1/2/3-4/6-8hrs post-dose), and predose for Cycle 0 Day 7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15 and from Cycle 2 onwards Day 1 and End of Treatment. Cycle 0 is 7 days and Cycle 1 and onwards is 28 days.

Study Arms (1)

IOA-289 in combination with gemcitabine/nab-paclitaxel

EXPERIMENTAL

Drug: IOA-289

Interventions

IOA-289 DRUG

IOA-289 will be administered orally twice daily (BID), starting from C0D1. Gemcitabine and nab-paclitaxel will be administrated by IV infusion, weekly for 3 weeks of a 4 week cycle starting at C1D1.

Also known as: gemcitabine, nab-paclitaxel, Abraxane

IOA-289 in combination with gemcitabine/nab-paclitaxel

Eligibility Criteria

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

You may qualify if:

• ≥18 years of age inclusive, at the time of signing the informed consent.
• Capable of giving signed informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Patients with histologically or cytologically confirmed metastatic unresectable pancreatic adenocarcinoma.
• Have measurable disease (≥ 1 measurable lesion) based on Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 as determined by the site study team.
• Eligible to receive 1st line systemic treatment with gemcitabine/nab-paclitaxel for metastatic disease.
• Baseline CA19-9 levels are available from a sample acquired no more than 4 weeks prior to screening.
• No prior systemic anti-cancer therapy for metastatic pancreatic cancer.
• Male subjects with female partners of childbearing potential, and female subjects of child-bearing potential who had a negative serum pregnancy test at screening, must agree to use a highly effective form of contraception (with at least 99% certainty) or avoid intercourse during and upon completion of the study and for at least 3 months after the last dose of study drug.

You may not qualify if:

• Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• Have prior significant medical history and AEs:
• Known active CNS metastases and/or carcinomatous meningitis.
• History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval \> 480 milliseconds is excluded (corrected by Fridericia).
• Known additional malignancy that is progressing or requires active treatment. Patients with active malignancy requiring concurrent intervention or previous malignancies (for example non-melanoma skin cancers, and in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
• Treatment with anticancer medications, investigational drugs, surgery and/or radiation within the following interval before the first administration of study drug:
• \< 14 days for chemotherapy, targeted small-molecule therapy, surgical resection of lesions or radiation therapy (prior palliative radiotherapy must have been completed at least 14 days prior to study drug administration). A 1-week washout is permitted for palliative radiation to non-CNS disease with Sponsor approval.
• Note: The use of denosumab against osteoporosis is permitted.
• \< 28 days for prior monoclonal antibody used for anticancer therapy with the exception of PD-1 pathway-targeted agents.
• \< 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices. For investigational agents with long half-lives (e.g., \> 5 days), enrolment before the fifth half-life requires Medical Monitor approval.
• Receiving an immune-suppressive based treatment for any reason (including chronic use of systemic corticosteroid at doses \> 10 mg/day prednisone equivalent) within 14 days prior to the first dose of study treatment (see the exception for CNS lesions described in 2a). Use of inhaled or topical steroids or brief corticosteroid use for radiographic procedures or systemic corticosteroids ≤ 10 mg is permitted.
• Have received a live vaccine within 30 days of planned start of study therapy.
• Have not recovered from toxic effect(s) of prior therapy to ≤ Grade 1, other than alopecia or fatigue.
• Known allergy or reaction to any component of either study drug or formulation components.

Sponsors & Collaborators

• iOnctura: lead

Study Sites (3)

UO Oncologia of Azienda Ospedaliera Universitaria Integrata di Verona

Verona, Verona, 37126, Italy

Location

Medical Oncology and Immunotherapy Unit, University Hospital of Siena

Siena, 53100, Italy

Location

Beatson West of Scotland Cancer Center

Glasgow, G12 0YN, United Kingdom

Location

Related Publications (1)

• Khasabova IA, Khasabov SG, Johns M, Juliette J, Zheng A, Morgan H, Flippen A, Allen K, Golovko MY, Golovko SA, Zhang W, Marti J, Cain D, Seybold VS, Simone DA. Exosome-associated lysophosphatidic acid signaling contributes to cancer pain. Pain. 2023 Dec 1;164(12):2684-2695. doi: 10.1097/j.pain.0000000000002967. Epub 2023 Jun 6.

  PMID: 37278638 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis; Neoplasms; Fibrosis

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Design

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

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 19, 2022
• Study Start: October 10, 2022
• Primary Completion: August 18, 2025
• Study Completion: August 18, 2025
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); IT (2)