OMX-0407 Phase I Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

iOmx Therapeutics AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Mar 2023 → 2 Apr 2026

Decision date (initial)

2024-09-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514554-75-00

EudraCT number

2022-002245-18

ClinicalTrials.gov

NCT05826600

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Dose response

Dose escalation phase:
The primary objective is to identify the DLTs
The secondary objectives are to:
• Identify the MTD of OMX-0407 and the recommended phase 2 dose (RP2D) of OMX-0407 if different from the MTD
• To investigate the safety and tolerability of OMX-0407
• To characterise the PK profile of OMX-0407

Cohort expansion phase:
The primary objective is to identify the objective response rate (ORR) of OMX-0407 in previously treated ccRCC, sqNSCLC, UC and AS (independent review for AS).
The secondary objectives are:
• To measure the duration of response (DoR) and progression-free survival (PFS)
• To measure overall survival (OS)
• To measure quality of life (QoL) using the EORTC QLQ-C30 questionnaire
• To further describe the safety and tolerability of OMX-0407
• To characterise the PK profile of OMX-0407
• To identify the ORR of OMX-0407 in unresectable previously treated AS by investigator assessment

Conditions and MedDRA coding

Previously treated unresectable solid tumours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. General Inclusion Criteria for both Dose Escalation and Cohort Expansion Phases : Age ≥18 years (≥16 years for the AS expansion cohort) and willing to provide informed consent for the study.
2. Cytological or pathological confirmation of advanced cancer.
3. Patients treated in three patient 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. Patients 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 patients must have received at least one previous line of systemic therapy for the tumour type under investigation. Patients who according to their treating physician are unsuitable for an existing licensed therapy are eligible for the study.
5. ECOG performance status 0, 1 or 2 for the dose escalation phase. Patients 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 patients 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 patients 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 patients 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 1 or stable (at least 3 weeks) Grade 2 (CTCAE v5.0).
9. Patients should have at least evaluable tumour by iRECIST criteria. Patients treated in the Cohort Expansion phases of the study must have measurable disease.
10. Additional Inclusion Criteria For Cohort Expansion Phase: ccRCC > Prior histological confirmation of ccRCC. In the case of mixed histology in order to be eligible at least 70% of reviewed tumour should be of clear cell histology.
11. Patients with known renal vascular involvement should be on stable anticoagulation at the start of treatment with OMX-0407. (Note: Tumour/skin biopsies should be performed prior to the onset of anticoagulation, if possible).
12. Previous treatment must include PD-1 blockade and VEGFR inhibition (unless contraindicated or not reimbursed).
13. Additional Inclusion Criteria for Cohort Expansion Phase: sqNSCLC > Prior histological confirmation of sqNSCLC. Patients with mixed histology tumours must have predominantly squamous histology (unless contraindicated or not reimbursed).
14. Previous treatment must include PD-1 blockade and platinum chemotherapy.
15. Patients with known oncogenic drivers including EGFR mutations ALK genomic rearrangements must have received prior directed therapy (unless contraindicated or not reimbursed)..
16. Additional Inclusion Criteria for Cohort Expansion Phase: UC > Prior histological confirmation of UC.
17. Previous treatment must include platinum-based chemotherapy PD-1 blockade and a Nectin A4 targeting agent (unless contraindicated or not reimbursed).
18. Additional Inclusion Criteria for Cohort Expansion Phase: AS > Clinical and histopathological confirmation of advanced/metastatic or unresectable visceral AS, cutaneous AS secondary to radiotherapy or other cutaneous AS.
19. Patients should have progressive disease (PD) according to the discretion of the investigator.
20. Patient has received at least one prior line of systemic therapy for metastatic or unresectable disease which must have included a taxane or an anthracycline (unless contraindicated or not reimbursed).
21. Willingness to undergo serial tumour biopsies before and during study treatment. Patient will still be eligible if the investigator deems the biopsy procedure to be an unacceptable health risk to the patient.

Exclusion criteria 17

1. Untreated CNS metastases. Patients 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. Patients with known CNS metastases must have received CNS directed therapy and not systemic therapy alone to be eligible for the study.
2. Allergy to OMX-0407 or any of its excipients.
3. 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. Patients with isolated increases in alkaline phosphatase (ALP) are eligible for the study.
4. Prothrombin Time or equivalent such as international normalized ratio (INR) or the Quick test > 1.5 ULN.
5. Activated partial thromboplastin time (PTT) > 1.5 ULN.
6. Chronic anticoagulant therapy that cannot be discontinued for tumour biopsy if necessary.
7. Treatment within 5 terminal half-lives (if known) or within the last 30 days prior to Day 1 of Cycle 1, whatever is shorter, with anti-cancer or investigational drugs.
8. Live vaccinations in the preceding four weeks of Day 1 of Cycle 1.
9. Persistent fever or other signs of uncontrolled infection.
10. Creatinine clearance by Cockcroft-Gault formula or local equivalent < 45 ml/min.
11. History of long QT syndrome.
12. History of ventricular arrhythmia within the last five years. 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. Left ventricular ejection fraction (LVEF) < 50%
15. QTcF of greater than 450 ms (men) or 460 ms (women) (mean of three readings performed two to five minutes apart).
16. Additional Exclusion Criteria for Cohort Expansion Phase: ccRCC > Uncontrolled hypertension defined as persistent blood pressure (BP) greater than diastolic 90 mm Hg and systolic 150 mm Hg
17. Additional Exclusion Criteria for Cohort Expansion Phase: ccRCC, sqNSCLC and UC > More than 3 previous lines of therapy in an unresectable or metastatic setting.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dose escalation phase : Incidence of DLTs attributable to OMX-0407 at each dose level. Cohort expansion phase : ORR. Tumour assessments will be performed at baseline and following every 12 weeks. For cutaneous AS cohort, images will be independently assessed. Responses will be defined according to immune-modified Response Evaluation Criteria in Solid Tumours (iRECIST).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

iOmx Therapeutics AG

Sponsor organisation

iOmx Therapeutics AG

Address

Fraunhoferstrasse 22, Martinsried Martinsried

City

Planegg

Postcode

82152

Country

Germany

Scientific contact point

Organisation

iOmx Therapeutics AG

Contact name

Tiantom Jarutat

Public contact point

Organisation

iOmx Therapeutics AG

Contact name

Tiantom Jarutat

Third parties 11

Locations

3 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications