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 Identifier:
F60089IV101
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study 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.
To evaluate VERT-002 for the treatment of cancer.
To evaluate PFL-002/VERT-002, an innovative targeted therapy intended to treat patients suffering from non-small cell lung cancer with alteration of the MET receptor.
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical efficacy of PFL-002/VERT-002, as a monotherapy for patients with MET-dependent tumors, including those emerging with acquired resistance to other treatments.
Part 1: To characterize the overall safety and tolerability of VERT-002 Part 1: To determine the selected range of doses for Part 2, the optimal biologically active dose (OBD) and the maximum tolerated dose (MTD) (or the maximum administered dose [MAD] if the MTD cannot be reached) and the administration schedule of VERT-002
Part 2a: To examine the preliminary activity of VERT-002 Part 2b: To determine the Recommended Phase 2 Dose (RP2D) of VERT-002 Part 2: To further characterize the overall safety and tolerability of VERT-002
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Solid Tumor
Unmapped
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: VERT-002 (PFL-002)
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Drug: Part 2a: Preliminary Activity Assessment (Phase Ib): One dose & schedule selected from Part 1
Drug: 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]
Drug: Part 3: Dose Expansion at RP2D (Phase II): To be de
Drug: Drug: VERT-002
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Part 1: histological confirmation of relapsed and/or refractory locally advanced or metastatic solid tumor for which no standard of care treatment is available.
- Part 2: histological confirmation of locally advanced or metastatic NSCLC Stage IIIB/C or IV (American Joint Commission on Cancer [AJCC] 8th edition) in participants who are not eligible for or should have received available standard of care therapies including curative intent surgery, chemoradiation, radiotherapy or systemic therapy.
- Part 1: presence of at least one of the following MET alterations based on local documentation of blood or archived tissue results:
- METex14 mutation
- MET kinase domain activating gene mutations (e.g. H1094L/R/Y, D1228H/N/V, Y1230A/C/D/H)
- MET amplification
- Part 2-a: presence of METex14 mutation (based on local documentation of blood or archived tissue results) and for Part 2-b presence of at least one of the following MET alterations: METex14 mutation (based on local documentation of blood or archived tissue results), de novo MET amplification (based on local documentation of archived tissue results). Confirmation after enrollment in the trial will be performed by central testing from an archival tumor biopsy sample (either tissue block or at least 15 serial cut unstained slides of 5 μm, at least 20% tumor content). In case no archival biopsy is available for central testing, the patient must be willing to have a fresh tumor biopsy sample collected and the tumor biopsy should be deemed safe and feasible by the investigator.
- Part 2: at least one measurable target lesion according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- 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. Note: crizotinib will be considered a MET TKI.
- Part 2: a maximum of 3 prior lines of systemic therapies.
- Adequate hematologic function.
- Adequate hepatic function.
- Adequate renal function.
- Albumin ≥ 3 g/dL.
- Adequate coagulation function.
- Adequate cardiac function.
- 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.
- 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
- Part 2: Documented evidence by local testing of targetable oncogene driver mutations.
- History of a primary malignancy other than the cancer under trial (as defined for Parts 1 and 2) 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.
- 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.
- History of hypersensitivity to active or inactive ingredients of VERT-002, or drugs with a similar chemical structure or from a similar class.
- Active, bacterial, fungal, or viral infection, within 2 weeks prior to the first dose of VERT-002 (C1D1).
- 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.
- Impaired cardiovascular function or clinically significant cardiovascular disease (either active or within 6 months prior to signing main informed consent).
- Uncontrolled intercurrent illness including, but not limited to psychiatric illness or social situation that would limit compliance with trial requirements.
- Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD.
- Women who are pregnant or breastfeeding.
- 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).
- Live attenuated vaccine within 28 days prior to the first dose of VERT-002 (C1D1).
- 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.
- Major surgical procedure within 14 days of the first dose of VERT-002 (C1D1).
- 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.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START La Rioja
Logroño, La Rioja, Spain, 26006
Investigator
Maria de Miguel
Status
Will Be Recruiting
Condition(s) Treated at Site
Solid Tumor
Unmapped