A clinical trial to learn about the safety and effects of VERT-002, a new anticancer drug for the treatment of patients with advanced solid tumors including lung cancer harboring MET alterations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pierre Fabre Medicament

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Feb 2025 → ongoing

Decision date (initial)

2024-12-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pierre Fabre Médicament

External identifiers

EU CT number

2024-512760-64-00

ClinicalTrials.gov

NCT06669117

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Dose response, Safety, Efficacy, Pharmacokinetic, Therapy

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

Secondary objectives 6

1. Part 1: To characterize the PK exposure profile of VERT-002
2. Part 1: To evaluate the immunogenicity of VERT-002
3. Part 1: To evaluate preliminary antitumor activity of increasing dose levels of VERT-002
4. Part 2: To assess the antitumor activity of VERT-002 at selected dose levels
5. Part 2: To further characterize the PK exposure profile of VERT-002
6. Part 2: To evaluate the immunogenicity of VERT-002

Conditions and MedDRA coding

locally advanced or metastatic solid tumors with MET alterations

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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, which applies in the following situations: - The participant is unsuitable for standard of care SoC) due to specific reasons. - No standard of care therapy is available for the participant. - The participant has already received all available standard of care therapies.
3. Part 1: presence of at least one of the following MET alterations based on local documentation of archival blood or archived tissue results: - METex14 mutation. - MET kinase domain activating gene mutations (e.g. H1094L/R/Y, D1228H/N/V, 1230A/C/D/H). - MET amplification. MET amplification positivity criteria are defined by methods specified in the protocol.
4. Part 2-a: presence of METex14 mutation (based on local documentation of blood or archived tissue results) 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).
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 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 for locally advanced or metastatic disease (that may or not include prior MET TKI, regardless of the line of treatment and regardless of the MET TKI (being combined or not) is allowed.
9. Adequate hematologic function prior to the first dose of VERT-002 as defined by the laboratory parameters specified in the protocol.
10. Albumin ≥ 3 g/dL.
11. Adequate cardiac function as defined in the protocol.

Exclusion criteria 6

1. Parts 2: Documented evidence by local testing of targetable oncogene driver mutations including MET fusion, KRAS, EGFR, ALK, ROS1. Note: For patients who are MET TKI pre-treated, pre-screening through tumor or liquid biopsy after the most recent progression is recommended to identify potential co-actionable oncogene driver mutations. The oncogene driver mutations considered as targetable are: EGFR exon19del, EGFR L858R, EGFR T790M, ALK rearrangements, ALK translocations, ROS1 translocations, BRAF V600 mutations, NTRK rearrangements, RET rearrangements, KRAS G12C, HER2 mutations.
2. History of a primary malignancy other than the cancer under trial (as defined for Parts 1 and2) 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 as specified in the protocol.
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. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for 2 weeks prior to enrollment in the trial.
4. Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis that requires steroid treatment, or any evidence of clinically active ILD.
5. Prior anticancer therapy as specified in the protocol.
6. For skin biopsy: participants who have received, are receiving, or are expected to receive therapeutic ultraviolet (UV) treatment before the skin biopsy, or who have experienced excessive UV exposure prior to the biopsy, as UV exposure may alter lesion characteristics and potentially confound biomarkers analyses. Note: this criterion applies only to participants who have provided informed consent for the optional skin biopsy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Part 1: Safety: Incidence and severity of Treatment Emergent Adverse Events (TEAEs)/Treatment Emergent Serious Adverse Events (TESAEs) including changes in laboratory values, physical examination, Eastern Cooperative Oncology Group (ECOG) performance status, vital signs and electrocardiogram (ECG) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria (NCI 2017).
2. Part 1: Tolerability: TEAEs/TESAEs leading to VERT-002 dose reductions, interruptions, and discontinuations.
3. Part 1: OBD: Pharmacokinetics (PK) exposures, pharmacodynamics, Objective Response Rate (ORR). Type, incidence, and severity of TEAEs/TESAEs according to NCI CTCAE 5.0 criteria (NCI 2017).
4. Part 1: MTD: Number and proportion of participants with locally advanced or metastatic solid tumors (including NSCLC) who experienced at least 1 Dose Limiting Toxicity (DLT) during cycle 1 i.e. the first 28 days of treatment per dose level.
5. Part 2: ORR and cORR, PK exposures, PDs.
6. Part 2: Overall safety, PK exposures, PDs and cORR.
7. Part 2: Safety: Incidence and severity of TEAEs/TESAEs including changes in laboratory values, physical examination, ECOG, performance status, vital signs and ECG according to NCI-CTCAE v5.0 criteria.
8. Part 2: Tolerability: TEAEs/TESAEs leading to VERT-002 dose reductions, interruptions, and discontinuations.

Secondary endpoints 12

1. Part 1: Serum concentrations at selected time points and PK exposure parameters (e.g. Cmax, Tmax, AUC0-tau, AUC0-t, AUC0-∞, t½, kel, CL, Vss, Vd, Rac for Cmax and AUC, and Cthrough).
2. Part 1: Incidence, time-course, and titers of VERT-002 anti-drug antibodies (ADA) during the trial relative to prevalence of ADA signal at baseline.
3. Part 1: Analysis of relationship between ADA incidence and safety, PK, or selected pharmacodynamic (PDs) endpoints.
4. Part 1: Confirmed Objective Response Rate (cORR) defined as the percentage of participants with confirmed partial response (PR) or confirmed complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. per Investigator’s Review (IR).
5. Part 1: Disease control rate (DCR) based on RECIST v1.1 per IR, measured as percentage of participants with CR + PR + stable disease (SD) ≥ 16 weeks.
6. Part 1: Time To Response (TTR) according to RECIST v1.1 per IR.
7. Part 1: Duration Of Response (DOR) according to RECIST v1.1 per IR.
8. Part 2: DCR,TTR, DOR, Progression Free Survival (PFS) according to RECIST v1.1 per IR.
9. Part 2: Overall Survival (OS)
10. Part 2: Serum concentrations at selected time points and PK exposure parameters (e.g. Cmax, Tmax, AUC0-tau, AUC0-t, AUC0-∞, t½, kel, CL, Vss, Vd, Rac for Cmax and AUC, and Cthrough).
11. Part 2: Incidence, time-course, and titers of VERT-002 ADA during the trial relative to prevalence of ADA signal at baseline.
12. Part 2: Analysis of relationship between ADA incidence and safety, efficacy, PK, or selected PDs endpoints.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pierre Fabre Medicament

Sponsor organisation

Pierre Fabre Medicament

Address

Les Cauquillous

City

Lavaur

Postcode

81500

Country

France

Scientific contact point

Organisation

Pierre Fabre Medicament

Contact name

Medical Team

Public contact point

Organisation

Pierre Fabre Medicament

Contact name

Corporate Scientific and Medical Information

Third parties 7

Locations

6 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 102 files

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

Application history

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