Clinical trial NCT06669117: FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations
Official title: A First-In-Human (FIH) Phase I/II Open-label, Multicentre, Dose Escalation and Expansion Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors Including Non-small Cell Lung Cancer (NSCLC) Harboring Mesenchymal-Epithelial Transition (MET) Alterations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
MET Alteration
Keywords: Locally advanced or metastatic solid tumors
MET alteration
Non-small cell lung cancer
Lead sponsor: Pierre Fabre Medicament
Sponsor class: INDUSTRY
First posted: 2024-11-01
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety: All parts: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria.
timeFrame: Screening to Safety Follow-up (30 days post last dose)
measure: Tolerability: All parts: Incidence of TEAEs/SAEs leading to VERT-002 dose reduction, interruption or discontinuation.
timeFrame: From screening up to 13 months
measure: Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: From the start of trial treatment until end of Cycle 1 per dose level
measure: Part 1: Optimal Biologically Active Dose (OBD): Incidence on PK/PD and ORR (Objective Response Rate)
timeFrame: From the first VERT-002 intake up to 13 months
measure: Part2a: Preliminary activity assessment: ORR and cORR (Confirmed Objective Response Rate)
timeFrame: From the start of trial treatment up to 13 months
measure: Part2b: Recommended Phase 2 Dose (RP2D): Incidence on overall safety, PK, PDs and cORR
timeFrame: From the start of trial treatment up to 13 months
Secondary outcomes:
measure: Serum PK Parameter: Maximum Plasma Concentration (Cmax)
timeFrame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
measure: Serum PK Parameter: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau)
timeFrame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
measure: Serum PK Parameter: Accumulation Ratio (Rac) for Maximum Observed Concentration (Cmax) and Area Under The Concentration-Time Curve (AUC)
timeFrame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
measure: Serum PK Parameter: Minimum Observed Concentration (Cmin)
timeFrame: Part 1: Cycle 1 and Cycle 2 - Days 1,2,4,8,15 and 22; Cycle 3 onward Day 1 and EOT (up to 8 months). Part 2: Cycle 1 Days 1,8 and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 12 months). Each cycle is 28 Days
measure: Serum ADA Parameter: Incidence of VERT-002 anti- drug antibodies (ADA)
timeFrame: Parts 1 and 2: Cycle 1 Days 1,8, and 15; Cycle 2 Days 1 and 15; Cycle 3 onward Day 1; and EOT (up to 8 months). Each cycle is 28 Days
measure: All Parts: cORR (Confirmed Objective Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per Investigator's Reviewer (IR)
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
measure: All Parts: DCR (Disease Control Rate) based on RECIST version 1.1 per IR
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
measure: All Parts: TTR (Time To Response) according to RECIST version 1.1 per IR
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
measure: All Parts: Duration Of Response (DOR) according to RECIST v1.1 per IR
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
measure: Part 2: Progression Free Survival (PFS) according to RECIST v1.1 per IR
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
measure: Part 2: Overall Survival (OS)
timeFrame: From the start of the treatment to at least 80% of the participants have been followed up for 24 months
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Research Center
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Oncology Partners
state: Tennessee
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Marseille
country: France
facility: APHP de Marseille - Hôpital Nord
city: Saint-Herblain
country: France
facility: Institut de Cancerologie de Ouest (ICO) - Saint-Herblain
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Villejuif
country: France
facility: Gustave Roussy
city: Cologne
country: Germany
facility: Universitaet zu Koeln - Centrum fuer Integrierte Onkologie (CIO)
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Orbassano
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center (AMC)
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
References: