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: May 16, 2024
• Sponsor: iOmx Therapeutics AG
• Information provided by (Responsible Party): iOmx Therapeutics AG

Tracking Information

• First Submitted Date: March 14, 2023
• First Posted Date: April 24, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: March 30, 2023
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2024)

• Identify Dose Limiting Toxicities [ Time Frame: 4 weeks (1 cycle) ]
  Incidence of dose limiting toxicities at each dose level
• Identify objective response rate [ Time Frame: Every 12 weeks (3 cycles) ]
  Number of objective responses of OMX-0407 in patients with Renal Cell cancer, Non small cell lung cancer and urothelial cancer

Original Primary Outcome Measures (submitted: April 12, 2023)

Identify Dose Limiting Toxicities [ Time Frame: 4 weeks (1 cycle) ]

Incidence of dose limiting toxicities at each dose level

Current Secondary Outcome Measures (submitted: May 14, 2024)

• Maximum Tolerated Dose [ Time Frame: evaluated up to approximately 3 years ]
  Identify the maximum tolerated dose and recommended dose for Phase II based on toxicities at each dose level
• Investigate the safety and tolerability of OMX-0407 [ Time Frame: through study completion, estimated up to approximately 3 years ]
  Incidence and severity of adverse events at each dose level
• Pharmacokinetics (Cmax) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Maximum observed plasma concentration
• Pharmacokinetics (Tmax) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Time of maximum observed plasma concentration
• Pharmacokinetics (AUClast) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Area under the plasma concentration-time curve from time of dosing to the last quantifiable timepoint
• Pharmacokinetics (AUCinf) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Area under the plasma concentration-time curve from time of dosing to infinity
• Pharmacokinetics (% extrapolated-AUCinf) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  The percentage of AUCinf derived via extrapolation from Tlast
• Pharmacokinetics (t½) of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Terminal elimination half-life
• Measure Duration of Response [ Time Frame: every 12 weeks (3 cycles) ]
  Determine the median duration of response according to RECIST 1.1
• Measure Progression Free Survivial [ Time Frame: every 12 weeks (3 cycles) ]
  Determine the median time for progression free survival

Original Secondary Outcome Measures (submitted: April 12, 2023)

• 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
• 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
• Pharmacokinetics (Cmax) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
  Maximum observed plasma concentration
• Pharmacokinetics (Tmax) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
  Time of maximum observed plasma concentration
• 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
• 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
• Pharmacokinetics (% extrapolated-AUCinf) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
  The percentage of AUCinf derived via extrapolation from Tlast
• Pharmacokinetics (t½) of OMX-0407 [ Time Frame: evaluated up to approximately 1.5 years ]
  Terminal elimination half-life

Current Other Pre-specified Outcome Measures (submitted: May 14, 2024)

• Explore Target Kinase Inhibition [ Time Frame: evaluated up to approximately 3 years ]
  Changes in selected kinase activity and T cell subset analysis in circulating peripheral blood cells, skin and tumour biopsy material
• Explore and characterize the metabolites of OMX-0407 [ Time Frame: evaluated up to approximately 3 years ]
  Analysis of metabolites presence in serum blood samples

Original Other Pre-specified Outcome Measures (submitted: April 12, 2023)

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

Descriptive Information

• Brief Title: A Study of OMX-0407 in Patients With Previously Treated Solid Tumours That Can't be Removed Surgically
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Drug: OMX-0407

Dose escalation

Study Arms

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 5, 20 and 80mg.

Intervention: Drug: OMX-0407

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 14, 2024): 158
• Original Estimated Enrollment (submitted: April 12, 2023): 30
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Belgium, Spain

Administrative Information

• NCT Number: NCT05826600
• Other Study ID Numbers: OMX-0407-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: iOmx Therapeutics AG
• Original Responsible Party: Same as current
• Current Study Sponsor: iOmx Therapeutics AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: iOmx Therapeutics AG
• Verification Date: May 2024