MET Alteration, Solid Tumor
Conditions
Keywords
Locally advanced or metastatic solid tumors, MET alteration, Non-small cell lung cancer
Brief summary
The goal of this clinical trial is to investigate the safety, the activity of VERT-002 (PFL-002), and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.
Interventions
DRUGVERT-002
Route of Administration: Intravenous
Sponsors
Pierre Fabre Medicament
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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. 3. 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 4. 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. 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. Note: crizotinib will be considered a MET TKI. 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 (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. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: All parts: Incidence and severity of treatment emergent adverse events (TEAEs)/serious adverse events (SAEs), according to NCI-CTCAE v5.0 criteria. | Screening to Safety Follow-up (30 days post last dose) |
| Tolerability: All parts: Incidence of TEAEs/SAEs leading to VERT-002 dose reduction, interruption or discontinuation. | From screening up to 13 months |
| Part 1: Maximum Tolerated Dose (MTD): Incidence of Dose-Limiting Toxicities (DLTs) | From the start of trial treatment until end of Cycle 1 per dose level |
| Part 1: Optimal Biologically Active Dose (OBD): Incidence on PK/PD and ORR (Objective Response Rate) | From the first VERT-002 intake up to 13 months |
| Part2a: Preliminary activity assessment: ORR and cORR (Confirmed Objective Response Rate) | From the start of trial treatment up to 13 months |
| Part2b: Recommended Phase 2 Dose (RP2D): Incidence on overall safety, PK, PDs and cORR | From the start of trial treatment up to 13 months |
Secondary
| Measure | Time frame |
|---|---|
| All Parts: DCR (Disease Control Rate) based on RECIST version 1.1 per IR | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
| All Parts: TTR (Time To Response) according to RECIST version 1.1 per IR | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
| Serum PK Parameter: Maximum Plasma Concentration (Cmax) | 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 |
| Part 2: Progression Free Survival (PFS) according to RECIST v1.1 per IR | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
| Part 2: Overall Survival (OS) | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
| All Parts: Duration Of Response (DOR) according to RECIST v1.1 per IR | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
| Serum PK Parameter: PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Dosing Interval (AUC0-tau) | 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 |
| Serum PK Parameter: Accumulation Ratio (Rac) for Maximum Observed Concentration (Cmax) and Area Under The Concentration-Time Curve (AUC) | 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 |
| Serum PK Parameter: Trough Concentration (Ctrough) | 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 |
| Serum ADA Parameter: Incidence of VERT-002 anti- drug antibodies (ADA) | 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 |
| All Parts: cORR (Confirmed Objective Response Rate) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 per Investigator's Reviewer (IR) | From the start of the treatment to at least 80% of the participants have been followed up for 24 months |
Countries
Belgium, France, Germany, Italy, Netherlands, South Korea, Spain, Taiwan, United States
Contacts
Primary ContactMedical Officer
Outcome results
None listed