A Study of OMX-0407 in Patients With Previously Treated Solid Tumours That Can't be Removed Surgically

• ClinicalTrials.gov Identifier: NCT05826600
• Recruitment Status: Recruiting
• First Posted: April 24, 2023
• Last Update Posted: November 8, 2023
• Sponsor: iOmx Therapeutics AG
• Information provided by (Responsible Party): iOmx Therapeutics AG

Study Description

Brief Summary:

The main purpose of this study is to determine the safety of different doses of OMX-0407. The study will also evaluate how the drug is distributed and exits the human body.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: OMX-0407	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Dose Escalation Study of OMX-0407 a Salt-inducible Kinase Inhibitor in Patients With Previously Treated Unresectable Solid Tumours
• Actual Study Start Date: March 30, 2023
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: May 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: OMX-0407; A starting daily dose of 20 mg OMX-0407 per participant split into twice daily 10 mg. Dose escalation will be determined by the safety monitoring committee. Capsule strengths 1, 5 and 20mg.	Drug: OMX-0407; Dose escalation

Outcome Measures

Primary Outcome Measures :

1. Identify Dose Limiting Toxicities [ Time Frame: 4 weeks (1 cycle) ]
   Incidence of dose limiting toxicities at each dose level

Secondary Outcome Measures :

1. Maximum Tolerated Dose [ Time Frame: evaluated up to approximately 1.5 years ]
   Identify the maximum tolerated dose and recommended dose for Phase II based on toxicities at each dose level
2. Investigate the safety and tolerability of OMX-0407 [ Time Frame: through study completion, estimated up to approximately 2.5 years ]
   Incidence and severity of adverse events at each dose level
3. Pharmacokinetics (Cmax) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   Maximum observed plasma concentration
4. Pharmacokinetics (Tmax) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   Time of maximum observed plasma concentration
5. Pharmacokinetics (AUClast) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   Area under the plasma concentration-time curve from time of dosing to the last quantifiable timepoint
6. Pharmacokinetics (AUCinf) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   Area under the plasma concentration-time curve from time of dosing to infinity
7. Pharmacokinetics (% extrapolated-AUCinf) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   The percentage of AUCinf derived via extrapolation from Tlast
8. Pharmacokinetics (t½) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
   Terminal elimination half-life

Other Outcome Measures:

1. Explore Target Kinase Inhibition [ Time Frame: evaluated up to approximately 1.5 years ]
   Changes in selected kinase activity and T cell subset analysis in circulating peripheral blood cells and tumour biopsy material

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years and willing to provide informed consent for the study.
2. Cytological or pathological confirmation of advanced cancer.
3. Subjects treated in three subject cohorts onwards will be required to provide either archival tumour material or be willing to undergo a core biopsy to provide tumour material during screening.
4. Subjects should have completed or be unsuitable for licensed therapies for their primary cancer unless such therapies are not available according to local practice - for example not reimbursed or included in treatment guidelines. All subjects must have received at least one previous line of systemic therapy for the tumour type under investigation. Subjects who have declined treatment or according to their treating physician are unsuitable for an existing licensed therapy are eligible for the study.
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1 or 2.
6. Able to swallow oral medication with no existing evidence of underlying gastrointestinal malabsorption or abnormal gastrointestinal transit.

7. For female subjects and male partners of childbearing potential, willingness and able to use two forms of highly effective contraception methods (e.g., oral contraceptive and condom, intra-uterine device, and condom) while on study and for 30 days after the last study treatment. For male subjects and female partners of childbearing potential, willingness and able to use two forms of highly effective contraception methods (e.g., oral contraceptive and condom, intra-uterine device, and condom) while on study and for 3 months after the last study treatment.

   Women who last experienced menses more than one year previously or who have undergone bilateral ovariectomy, hysterectomy or tubal ligation which is documented in their medical notes do not require to use contraception during or after treatment with OMX-0407.

   Male subjects who have previously undergone vasectomy are not required to use contraception.

8. All toxicity from previous anti-cancer therapy including radiotherapy must have recovered to either Grade I or stable Grade II (CTCAE v5).
9. Subjects should have at least evaluable tumour by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.

Exclusion Criteria:

1. Untreated Central Nervous System (CNS) metastases. Subjects with CNS metastases that have completed treatment at least two weeks previously and have either an unchanging or no neurological deficit whilst not receiving corticosteroid therapy are eligible. Subjects with known CNS metastases must have received CNS directed therapy and not systemic therapy alone to be eligible for the study.
2. Either Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 2.5 upper limit of normal (ULN) unless in the presence of hepatic metastases when AST or ALT as high as 5 ULN is acceptable. Serum bilirubin > 1.5 ULN unless in the presence of hepatic metastases when serum bilirubin as high as 3 x ULN is acceptable. Subjects with isolated increases in alkaline phosphatase (ALK) are eligible for the study.
3. Prothrombin Time or equivalent such as international normalized ratio (INR) or the Quick test > 1.5 ULN.
4. Activated Partial Thromboplastin Time (PTT) > 1.5 ULN.
5. Chronic anticoagulant therapy that cannot be discontinued for tumour biopsy if necessary.
6. Previous biological or unlicensed anticancer therapy within five half-lives or thirty days of treatment - whichever is shortest.
7. Prior cytotoxic chemotherapy in the preceding three weeks.
8. Persistent fever or other signs of uncontrolled infection.
9. Creatinine clearance by Cockcroft-Gault formula or local equivalent < 30 ml/min.
10. Allergy to OMX-0407 or any of its excipients.
11. Personal or family history of long QT syndrome or sudden death.
12. Family or personal history of ventricular arrythmia. Known untreated aberrant preexcitation pathways such as Wolf-Parkinson-White syndrome. Ongoing atrial fibrillation unless the ventricular rate is controlled by medical therapy.
13. Unstable hypertension requiring changes in antihypertensive medication within the preceding three months, Myocardial Infarction or Cerebrovascular accident within the preceding three months. Cardiac failure New York Heart Association (NYHA) Grade III or IV.
14. Abnormal echocardiogram (ECHO) according to investigational site criteria including a normal Ejection Fraction.
15. Corrected QT interval (QTc) after Fridericia correction of greater than 450 ms (man) or 460 ms (woman) (mean of three readings performed at least five minutes apart).
16. Second degree Atrioventricular block or cardiac pacemaker.
17. Subject must have fully recovered from major surgery such as thoracotomy. Open biopsy or insertion of a venous access device does not constitute major surgery.
18. Known active Hepatitis B (HBV) or C (HCV) including subjects receiving antiviral therapy. Subjects with a history of hepatitis are eligible for the study if they are positive for anti-HBs or do not have detectable HCV messenger ribonucleic acid (mRNA) at least six weeks from completing antiviral therapy.
19. Ongoing systemic disease such chronic obstructive pulmonary disease (COPD) or depression or other psychiatric illnesses which may reduce study compliance.
20. Ongoing drug dependence or parenteral substance abuse.
21. Concurrent use of medications at risk of Torsade de pointes under normal clinical usage.
22. Live vaccinations in the preceding four weeks.
23. Subjects who have received treatment for another malignancy in the preceding three years other than squamous cell or basal cell carcinoma of the skin, Carcinoma In Situ of the uterine cervix, Ductal Carcinoma In Situ of the breast, non-muscle invasive carcinoma of the bladder, melanoma in situ or adenocarcinoma of the prostate (Gleason score of five or less).

24. Myelosuppression defined as any of the below:

    Haemoglobin <9.5 g/dl White Cell Count <2 x 1000 per µl Neutrophils <1.5 x 1000 per µl Platelets <75 000 per µl Independent of haematopoietic growth factors and transfusion

25. Receipt of any other investigational agent within 28 days prior to first administration of OMX-0407.
26. Female subjects must not be pregnant or breast feeding

Contacts and Locations

Contacts

Contact: Murray Yule, MD; +49 (0)89 8999 7090 0; murray.yule@iomx.com

Locations

Spain

NEXT Oncology - Hospital Quironsalud Barcelona; Recruiting

Barcelona, Spain

Contact: Garralda, MD

START Madrid - Hospital Fundacion Jimenez Diaz; Recruiting

Madrid, Spain, 28040

Contact: Moreno, MD

Centro Integral Oncológico Clara Campal; Recruiting

Madrid, Spain, 28050

Contact: Calvo, MD

NEXT Oncology - Hospital Universitario Quironsalud; Recruiting

Madrid, Spain

Contact: Boni, MD

Sponsors and Collaborators

iOmx Therapeutics AG

More Information

• Responsible Party: iOmx Therapeutics AG
• ClinicalTrials.gov Identifier: NCT05826600
• Other Study ID Numbers: OMX-0407-101
• First Posted: April 24, 2023
• Last Update Posted: November 8, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms