ZENOCUTUZUMAB for Solid tumour | Non-small cell lung cancer | Pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- 1. Age ≥18 years"}
• {"criterion_text":"- 10. Negative pregnancy test results available as defined by a blood human chorionic gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry); NOTE: Women with amenorrhea associated with prior treatment with antineoplastic medications are still considered as being of child-bearing potential."}
• {"criterion_text":"- 11. Sexually active male and female patients of childbearing potential must agree to use one of the highly effective methods of birth control during entire study and 6 months after final administration of MCLA-128"}
• {"criterion_text":"- 12. Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice;"}
• {"criterion_text":"- 13. Capable of understanding the mandated and optional protocol requirements, is willing and able to comply with the study protocol procedures and has signed the main informed consent document. For any optional biopsy sampling (tissue and/or blood) and long-term sample storage, additional consent is required;"}
• {"criterion_text":"- 14. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy or no satisfactory alternative treatment options are available; NOTE – South Korea, Germany and Austria only: patients must have received prior standard therapy appropriate for their tumor type and stage of disease."}
• {"criterion_text":"- 15. Histologic or cytologic diagnosis of locally-advanced unresectable or metastatic solid tumor malignancy with a documented NRG1 gene fusion, identified through molecular assays such as RNA/DNA-based sequencing assays, as routinely performed ast CLIA or other similarly-certified laboratories. The following tumor types are included: o Group F: NSCLC o Group G: pancreatic adenocarcinoma o Group H: any other solid tumor NOTE: Patients harboring fusions that are predicted to be non-functional, i.e.., lack of EGF-domain, will not be included in the study. The Sponsor will conduct a review of genomic results and may request collateral testing, approve, or deny the case."}
• {"criterion_text":"- 2. ≥1 measurable lesion, RECIST v1.1 or evaluable disease for a limited number of patients in group H"}
• {"criterion_text":"- 3. ECOG 0, 1 or 2"}
• {"criterion_text":"- 4. Life expectancy ≥12 weeks"}
• {"criterion_text":"- 5. Toxicities incurred as a result of previous anti-cancer therapy resolved to ≤Grade 1 except for alopecia, Grade 2 sensory neurotoxicity, or any other toxicity that in the opinion of the investigator does not affect the assessment of adverse events related to the study drug"}
• {"criterion_text":"- 6. Treatment with anti-cancer or investigational product within set intervals before first dose of MCLA-128: a.>14d or >5 half-lives prior to study entry, whichever is shorter. b.>14d for radiotherapy. Note: A less than 1-week wash-out period is permitted only for palliative radiation to non-CNS disease with Sponsor approval."}
• {"criterion_text":"- 7. Recovery from prior surgery/other procedure/ complication to ≤ Grade 2 or to baseline condition that in opinion of the investigator does not affect the assessment of adverse events related to the study drug."}
• {"criterion_text":"- 8. Laboratory values at Screenings: a.Absolute neutrophil count ≥1.5 x 10^9/L without colony stimulating factor support for at least 7 days prior to Screening. b.Platelets ≥75 x 10^9/L without transfusion support for at least 7 days prior to Screening. c.Hemoglobin ≥8 g/dL or ≥5 mmol/L. d.ALT, AST ≤3 x ULN and total bilirubin ≤1.5 x ULN. e.Estimated glomerular filtration rate (GFR) of >30 mL/min based on the Cockroft-Gault formula."}
• {"criterion_text":"- 9. Able to provide at baseline a mandatory tumor biopsy sample, preferably a block. If safe/feasible, a fresh FFPE biopsy sample is preferred; archival tissue is acceptable (preferably not more than 2 years old Note 1: For patients who received afatinib or other HER-targeting agents, a biopsy collected after the last line of treatment is strongly preferred to assess for mechanisms of acquired resistance Note 2: When archival tissue is not available and collection of a fresh biopsy is not safe or feasible during the screening period, these patients will be allowed to enroll in the MCLA128-CL01 trial provided they meet all other inclusion/exclusion criteria."}

Exclusion criteria

• {"criterion_text":"- 1. Pregnant or lactating;"}
• {"criterion_text":"- 2. Presence of an active uncontrolled infection or an unexplained fever greater than 38.5°C during Screening up to the first scheduled day of dosing. At the discretion of the Investigator, patients with tumor fever or a clinically insignificant minor infection may be enrolled (i.e. mild upper respiratory infection);"}
• {"criterion_text":"- 3. Known hypersensitivity to any of the components of MCLA-128 or history of severe hypersensitivity reactions to human or humanized monoclonal antibodies, including therapeutic antibodies;"}
• {"criterion_text":"- 4. Patients with the following infectious diseases are excluded: a. known HIV b. active Hepatitis B infection (HBsAg positive) without receiving antiviral treatment Note: • Patients with active hepatitis B (HBsAg positive) must receive antiviral treatment with lamivudine, tenofovir, entecavir, or other antiviral agents, starting at least ≥ 7 days before the initiation of the study treatment. • Patients with antecedents of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA negative) are eligible. c. positive test for Hepatitis C ribonucleic acid (HCV RNA) Note: • Patients in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained response after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the use of IFN-free regimens) or ≥ 12 months (with the use of IFN-based regimens) after cessation of antiviral treatment are eligible; NOTE: Patients without known or suspected HIV, Hepatitis B or Hepatitis C infection do not require specific viral testing during the screening period."}
• {"criterion_text":"- 5. Known symptomatic or unstable brain metastases. Patients with asymptomatic brain metastases are eligible to participate if the metastases have been radiographically and clinically stable for at least one month. If on steroids for this indication, the patient must be on a stable dose for at least one month."}
• {"criterion_text":"- 6. Patients with leptomeningeal metastases"}
• {"criterion_text":"- 7. Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative or palliative intent and in the opinion of the investigator, with sponsor agreement, the previous or concurrent malignancy condition doesn't affect the assessment of safety and efficacy of the study drug;"}
• {"criterion_text":"- 8. Presence of LVEF < 50% on the screening echocardiogram; or history or presence of any significant cardiovascular disease, including unstable angina or myocardial infarction within 12 months, prior to screening, congestive heart failure (NYHA Class III or IV), or ventricular arrhythmia requiring medication"}
• {"criterion_text":"- 9. Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results."}

Primary endpoints

• {"endpoint_text":"- Part 1: Evaluation of adverse events (AEs) and dose limiting toxicities (DLT).","definition_or_measurement_approach":"Assessment and recording of adverse events and identification of dose limiting toxicities during Part 1 (no further measurement detail provided in the record)."}
• {"endpoint_text":"- Part 2: Groups A - E, and F: • Frequency and nature of AEs. • Overall response rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (CBR)","definition_or_measurement_approach":"Frequency and nature of AEs collected; anti-tumor activity measured by ORR, DOR and CBR (measurement specifics not stated in this primary endpoint text)."}
• {"endpoint_text":"- Part 2: Groups F, G, H (NRG1 fusion): • ORR per RECIST v1.1 as per local Investigator's assessment. • DOR per RECIST v1.1 as per local Investigator's assessment.","definition_or_measurement_approach":"ORR and DOR assessed according to RECIST v1.1 by the local Investigator."}

Secondary endpoints

• {"endpoint_text":"- Part 1: 1. Frequency and nature of AEs/serious adverse events (SAEs). 2. Assessment of PK variables. 3. Incidence and serum titers of anti-drug antibodies against MCLA-128. 4. Anti-tumor activity and clinical benefit assessed by RECIST v1.1 determining ORR, DOR, progression-free survival (PFS) and survival.","definition_or_measurement_approach":"AEs/SAEs frequency and nature recorded; PK variables assessed (pharmacokinetic sampling); immunogenicity via anti-drug antibody incidence and serum titers; anti-tumor activity assessed by RECIST v1.1 to derive ORR, DOR, PFS and overall survival."}
• {"endpoint_text":"- Part 2: Groups A - E, and F : 5. Assessment of PK variables. 6. Population PK analysis. 7. Incidence and serum titers of anti-drug antibodies against MCLA-128.","definition_or_measurement_approach":"PK assessments including population PK analyses; measurement of anti-drug antibody incidence and titers in serum."}
• {"endpoint_text":"- Part 2: Groups F, G, H (NRG1 fusion): ORR per RECIST v1.1. CBR per RECIST v1.1. DOR per RECIST v1.1. Time to response per RECIST v1.1 Frequency and nature of AEs. Assessment of PK variables. Population PK analysis. Incidence and serum titers of anti-drug antibodies against MCLA-128.","definition_or_measurement_approach":"Tumor response endpoints (ORR, CBR, DOR, time to response) assessed per RECIST v1.1; AEs recorded; PK and population PK analyses; immunogenicity measured by anti-drug antibody incidence/titers."}

Sweden

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

10-12-2024

Processing Time Days

266

Number Of Sites

1

Number Of Participants

2

Denmark

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

09-12-2024

Processing Time Days

265

Number Of Sites

1

Number Of Participants

2

Belgium

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

09-12-2024

Processing Time Days

265

Number Of Sites

1

Number Of Participants

2

Norway

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

06-12-2024

Processing Time Days

262

Number Of Sites

1

Number Of Participants

5

Austria

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

15-12-2024

Processing Time Days

271

Number Of Sites

1

Number Of Participants

10

Netherlands

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

23-09-2025

Processing Time Days

553

Number Of Sites

2

Number Of Participants

50

Germany

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

554

Number Of Sites

3

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

554

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

628

Number Of Sites

2

Number Of Participants

150

France

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

16-04-2026

Processing Time Days

758

Number Of Sites

5

Number Of Participants

100

Primary sponsor

Full Name

Partner Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Fortrea Development Limited

Responsibilities

Monitoring, Regulatory (e.g. preparation of applications to CA and ethics committee), Data management, E-data capture, SUSAR reporting, Quality assurance auditing, Statistical analysis, Medical writing, Project Management

Third parties

• {"country":"United Kingdom","full_name":"Drug Development Solutions Limited","duties_or_roles":"PK, ADA Cytokines","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Caris Mpi Inc.","duties_or_roles":"DNA/RNA sequencing","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"LAP & P Consultants B.V.","duties_or_roles":"PopPK and exposure response analysis","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Medical image analysis/ blinded independent central review","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Firalis","duties_or_roles":"DNA/RNA sequencing; Proteomics OLINK","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Venn Life Sciences Ed B.V.","duties_or_roles":"Non-compartmental PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Biomarker sample management, NRG1 ISH, FCGR PCR (genotyping)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Sample storage/management, HER2 FISH, HER2 IHC (EU, Asia)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"Immunofluorescence assay","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"Monitoring, Regulatory (e.g. preparation of applications to CA and ethics committee), Data management, E-data capture, SUSAR reporting, Quality assurance auditing, Statistical analysis, Medical writing, Project Management","organisation_type":"Pharmaceutical company"}