A Phase I/II Study of MCLA-128, a full length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients with Solid Tumors (eNRGy)

JRCT ID: jRCT2031210483

Registered date:14/12/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: NSCLC, pancreatic adenocarcinoma and all other solid tumors with NRG1 fusion
• Date of first enrollment: 22/12/2020
• Target sample size: 25
• Countries of recruitment: Austria,Japan,Belgium,Japan,Denmark,Japan,France,Japan,Italy,Japan,theNetherlands,Japan,Spain,Japan,Norway,Japan,Germany,Japan,Sweden,Japan,United Kingdom,Japan,SouthKorea,Japan,Israel,Japan,Taiwan,Japan,Singapore,Japan,Canada,Japan,United States,Japan
• Study type: Interventional
• Intervention(s): 750 mg of MCLA-128 is given intravenously every 2 weeks for 2 hours.

Outcome(s)

• Primary Outcome: Overall response rate per RECIST v1.1 as per local Investigators assessment.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Age 18 years or older;
2. At least one measurable lesion according to RECIST v1.1 OR evaluable disease for a limited number of patients (up to 15) in Group H;
3. Performance status of ECOG 0, 1 or 2;
4. Estimated life expectancy of at least 12 weeks;
5. Toxicities incurred as a result of previous anti-cancer therapy resolved to <=Grade 1 (as defined by NCI CTCAE v4.03)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;
6. Treatment with anti-cancer medication or investigational drugs within the following intervals before the first dose of MCLA-128:
a. >14 days or >5 half-lives prior to study entry, whichever is shorter.
b. >14 days for radiotherapy. Note: A less than 1-week wash-out period is permitted only for palliative radiation to non-CNS disease with Sponsor approval.
7. Patient has recovered from prior surgery or other procedure or 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;
8. Laboratory values at Screening:
a. Absolute neutrophil count >=1.5 x 109/L without colony stimulating factor support for at least 7 days prior to Screening;
b. Platelets >=75 x 109/L without transfusion support for at least 7 days prior to Screening;
c. Hemoglobin >=8 g/dL or >=5 mmol/L;
d. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <=3 x upper limit of normal (ULN) and total bilirubin <=1.5 x ULN; in cases of metastatic liver involvement, ALT/AST <=5 x ULN and total bilirubin <=2 x ULN will be allowed; isolated elevation of AST or ALT > 3 x ULN in the absence of underlying liver disease may be considered for enrollment upon Sponsor review and approval; in cases of antecedents of Gilberts syndrome when total bilirubin <=3.0 x ULN or direct bilirubin <=1.5 x ULN will be allowed;
e. Estimated glomerular filtration rate (GFR) of >30 mL/min based on the Cockroft-Gault formula;
9. Able to provide at baseline a mandatory tumor biopsy sample (FFPE), 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: For patients with a locally confirmed NRG1 gene fusion, 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 MCLA-128-CL01 trial provided they meet all other inclusion/exclusion criteria.
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.;
11. Sexually active male and female patients of childbearing potential must agree to use one of the following highly effective methods of birth control during the entire duration of the study and for 6 months after final administration of MCLA-128:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
oral, intravaginal, transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation 1:
oral, injectable, implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
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;
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;
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;
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 next generation sequencing-based assays [DNA or RNA], as routinely performed at CLIA or other similarly-certified laboratories. The following tumor types are included:
Group F: NSCLC
Group G: pancreatic adenocarcinoma
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. For equivocal cases, including those with NRG1 as the upstream partner, the Sponsor will manually review genomic results and may request collateral testing, approve, or deny the case.

Exclude criteria

1. Pregnant or lactating;
2. Presence of an active uncontrolled infection or an unexplained fever greater than 38.5 Celsius degree 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);
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;
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.
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;
6. Patients with leptomeningeal metastases;
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;
8. Presence of congestive heart failure or 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;
9. Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patients ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.

Related Information

• Primary Sponsor: Wasserman Ernesto
• Secondary ID(s): NCT02912949