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

Solid Tumor Clinical Trial

Official title:

A Phase I/Ib Dose Escalation and Cohort Expansion Study of OMX-0407 a Salt-inducible Kinase Inhibitor in Patients With Previously Treated Unresectable Solid Tumours

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05826600
• Other study ID #: OMX-0407-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 30, 2023
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: iOmx Therapeutics AG
• Contact: Murray Yule, MD
• Phone: +49 (0)89 8999 7090 0
• Email: murray.yule[@]iomx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: April 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

General Inclusion Criteria for all subjects:

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. Subjects treated in the cohort expansion phase of the study should have an ECOG Performance status of 0 or 1.

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. Subjects treated in the Cohort Expansion phases of the study should have measurable disease

Additional Inclusion Criteria for ccRCC:

1. Prior histological confirmation of clear cell renal cell carcinoma. In the case of mixed histology in order to be eligible at least 70% of reviewed tumour should be of clear cell histology.

2. Subjects with known renal vascular involvement should be on stable anticoagulation at the start of treatment with OMX-0407. Tumour/skin biopsies should be performed prior to the onset of anticoagulation.

3. Previous treatment must include PD-1 blockade and VEGFR inhibition.

Additional Inclusion Criteria for sqNSCLC:

1. Prior histological confirmation of sqNSCLC. Subjects with mixed histology tumours must have predominantly squamous histology.

2. Previous treatment must include PD-1 blockade and platinum chemotherapy.

3. Patients with known oncogenic drivers including EGFR mutations ALK genomic rearrangements must have received prior directed therapy.

Additional Inclusion Criteria for UC:

1. Prior histological confirmation of UC

2. Previous treatment must include platinum-based chemotherapy PD-1 blockade and a Nectin A4 targeting agent.

General Exclusion Criteria for all Subjects:

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 disabling 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 Additional Exclusion Criteria for ccRCC 1. Uncontrolled hypertension defined as persistent BP greater than Diastolic 90 mm Hg and Systolic 150 mm Hg Additional Exclusion Criteria for: ccRCC, sqNSCLC, and UC

1. More than 3 previous lines of therapy in a metastatic setting (excluding therapy given in the neoadjuvant/adjuvant setting

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• OMX-0407
Dose escalation

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Spain	NEXT Oncology - Hospital Quironsalud Barcelona	Barcelona
Spain	Centro Integral Oncológico Clara Campal	Madrid
Spain	NEXT Oncology - Hospital Universitario Quironsalud	Madrid
Spain	START Madrid - Hospital Fundacion Jimenez Diaz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
iOmx Therapeutics AG

Countries where clinical trial is conducted

Belgium,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Explore Target Kinase Inhibition	Changes in selected kinase activity and T cell subset analysis in circulating peripheral blood cells, skin and tumour biopsy material	evaluated up to approximately 3 years
Other	Explore and characterize the metabolites of OMX-0407	Analysis of metabolites presence in serum blood samples	evaluated up to approximately 3 years
Primary	Identify Dose Limiting Toxicities	Incidence of dose limiting toxicities at each dose level	4 weeks (1 cycle)
Primary	Identify objective response rate	Number of objective responses of OMX-0407 in patients with Renal Cell cancer, Non small cell lung cancer and urothelial cancer	Every 12 weeks (3 cycles)
Secondary	Maximum Tolerated Dose	Identify the maximum tolerated dose and recommended dose for Phase II based on toxicities at each dose level	evaluated up to approximately 3 years
Secondary	Investigate the safety and tolerability of OMX-0407	Incidence and severity of adverse events at each dose level	through study completion, estimated up to approximately 3 years
Secondary	Pharmacokinetics (Cmax) of OMX-0407	Maximum observed plasma concentration	evaluated up to approximately 3 years
Secondary	Pharmacokinetics (Tmax) of OMX-0407	Time of maximum observed plasma concentration	evaluated up to approximately 3 years
Secondary	Pharmacokinetics (AUClast) of OMX-0407	Area under the plasma concentration-time curve from time of dosing to the last quantifiable timepoint	evaluated up to approximately 3 years
Secondary	Pharmacokinetics (AUCinf) of OMX-0407	Area under the plasma concentration-time curve from time of dosing to infinity	evaluated up to approximately 3 years
Secondary	Pharmacokinetics (% extrapolated-AUCinf) of OMX-0407	The percentage of AUCinf derived via extrapolation from Tlast	evaluated up to approximately 3 years
Secondary	Pharmacokinetics (t½) of OMX-0407	Terminal elimination half-life	evaluated up to approximately 3 years
Secondary	Measure Duration of Response	Determine the median duration of response according to RECIST 1.1	every 12 weeks (3 cycles)
Secondary	Measure Progression Free Survivial	Determine the median time for progression free survival	every 12 weeks (3 cycles)