FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations

Pierre Fabre

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; MET Alteration

Treatments: Drug: VERT-002

Study type: Interventional

Funder types: Industry

Identifiers

NCT06669117

F60089IV101

2024-512760-64-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The goal of this clinical trial is to investigate the safety, the activity of VERT-002, and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Part 1: histological confirmation of relapsed and/or refractory locally advanced or metastatic solid tumor for which no standard of care treatment is available.

2. Part 2: histological confirmation of locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) Stage IIIB/C or IV (American Joint Commission [AJCC] 8th edition) not eligible for curative intent surgery, chemoradiation or radiotherapy.

3. Part 1: presence of at least one of the following Mesenchymal-Epithelial Transition (MET) alterations documented locally on archival blood or tissue sample:

   • METex14 mutation
   • MET kinase domain activating gene mutations (e.g. H1094L/R/Y, D1228H/N/V, Y1230A/C/D/H)
   • MET amplification

4. Part 2-a: presence of METex14 mutation and for Part 2-b presence of at least one of the following MET alterations: METex14 mutation, de novo MET amplification, documented locally (archived tissue sample). Confirmation after enrollment in the trial by central testing from an archival tumor biopsy. In case no archival biopsy is available for central testing, the patient must be willing to undergo a fresh tumor biopsy, and the tumor biopsy should be deemed safe and feasible by the investigator.

5. Part 2: at least one measurable target lesion according to RECIST v1.1.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

7. Part 1: participants may have received MET Tyrosine Kinase Inhibitor (TKI) as part of previous treatment, regardless of the line of therapy (first or second line), and regardless of the MET TKI being combined or not.

8. Part 2: a maximum of 3 prior lines of systemic therapies.

9. Adequate hematologic function.

10. Adequate hepatic function.

11. Adequate renal function.

12. Albumin ≥ 3 g/dL.

13. Adequate coagulation function.

14. Adequate cardiac function.

15. Female participants of childbearing potential must have a negative highly sensitive serum β-HCG test performed within 7 days prior to the first dose of VERT-002 and a negative urine pregnancy test performed at C1D1 prior to the first dose of VERT-002.

16. Male participants/partners with female spouse/partners of childbearing potential must agree to take appropriate precautions to avoid fathering a child.

NOTE: Other protocol defined inclusion criteria may apply.

Exclusion criteria

1. Part 2: Documented evidence by local testing of targetable oncogene driver mutations.

2. History of a primary malignancy other than the cancer under trial with the exception of:

   • Participants with a previous malignancy who completed their anticancer treatment at least 2 years before signing informed consent and with no evidence of residual disease from the prior malignancy at screening.
   • Malignancies with a negligible risk of metastasis or death (i.e. 5-year overall survival rate > 90%) that are adequately treated.

3. Uncontrolled Central Nervous System (CNS) metastases or spinal cord compression that are associated with progressive neurological symptoms or require increasing doses of corticosteroids to control the CNS disease.

4. History of hypersensitivity to active or inactive ingredients of VERT-002, or drugs with a similar chemical structure or from a similar class.

5. Active, bacterial, fungal, or viral infection, within 2 weeks prior to the first dose of VERT-002 (C1D1).

6. Positive SARs-CoV-2 or variants of SARs-CoV2 test within 2 weeks prior to first dose administration of VERT-002 (C1D1) or with suspected infection with SARs-CoV-2 or variants of SARs-CoV-2 and confirmation pending.

7. Impaired cardiovascular function or clinically significant cardiovascular disease (either active or within 6 months prior to signing main informed consent).

8. Uncontrolled intercurrent illness including, but not limited to psychiatric illness or social situation that would limit compliance with trial requirements.

9. Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD.

10. Women who are pregnant or breastfeeding.

11. Prior anticancer therapy:

    • MET TKI within 7 days prior to the first dose of VERT-002,
    • Any other systemic anticancer therapy within 28 days or 5 half-lives of the anticancer therapy whichever is the shortest, but with a minimum of 14 days interval, prior to the first dose of VERT-002 (C1D1),
    • Radiotherapy to a large field or including a vital organ (including whole brain radiotherapy or stereotactic radiosurgery to brain) within 14 days prior to the first dose of VERT-002 (C1D1).

12. Live attenuated vaccine within 28 days prior to the first dose of VERT-002 (C1D1).

13. Any toxicities from prior therapy with NCI- CTCAE Grade > 1 at the time of the first dose administration of VERT-002 (C1D1). Exceptions include any grade alopecia, fatigue and peripheral neuropathy with a grade ≤ 2.

14. Major surgical procedure within 14 days of the first dose of VERT-002 (C1D1).

15. Participation in a clinical trial with administration of an investigational drug within 5 half- lives plus 14 days of the investigational drug, prior to the first dose of VERT-002 (C1D1).

NOTE: Other protocol defined exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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140 participants in 1 patient group

VERT-002

Experimental group

Description:

Part 1: Dose escalation (Phase Ia): VERT-002 will be administered via intravenous (IV) infusion every 2 weeks. 4 provisional doses are planned. An alternative regimen may be tested informed by the emerging data Part 2a: Preliminary Activity Assessment (Phase Ib): One dose \& schedule selected from Part 1 Part 2b: Dose range optimization (Phase Ib): 2 or 3 doses \& schedule selected from Part 1: From the lower limit \[Optimal Biologically Active Dose (OBD)\] \& upper limit \[Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) if MTD is not reached\] Part 3: Dose Expansion at RP2D (Phase II): To be defined later on

Treatment:

Drug: VERT-002