2024-512358-78-00招募中2 期
A Phase I/II Study of MCLA-128, a full length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients with Solid Tumors (eNRGy)
Partner Therapeutics Inc., Partner Therapeutics Inc.18 个研究点 分布在 10 个国家目标入组 341 人开始时间: 2024年4月2日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 341
- 试验地点
- 18
- 主要终点
- Part 1: Evaluation of adverse events (AEs) and dose limiting toxicities (DLT).
研究概览
简要总结
Part 1:
- Determination of the maximum tolerated dose (MTD) and/or maximum recommended dose (MRD) of MCLA-128. Part 2: Groups A – E, and F
- To characterize the safety and tolerability of MCLA-128
- To explore the relationships between the anti-tumor activity of MCLA-128 and disease-related biomarkers. Part 2: Groups F, G, H (NRG1 fusion)
- To assess the magnitude of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally
- To assess durability of anti-tumor activity of MCLA-128 in patients with NRG1 fusions as assessed locally.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years
- •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.
- •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
- •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informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice;
- •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;
- •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.
- •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.
- •≥1 measurable lesion, RECIST v1.1 or evaluable disease for a limited number of patients in group H
- •ECOG 0, 1 or 2
- •Life expectancy ≥12 weeks
- •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
- •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.
- •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.
- •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.
- •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.
排除标准
- •Pregnant or lactating;
- •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);
- •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;
- •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.
- •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.
- •Patients with leptomeningeal metastases
- •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;
- •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
- •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.
结局指标
主要结局
Part 1: Evaluation of adverse events (AEs) and dose limiting toxicities (DLT).
Part 1: Evaluation of adverse events (AEs) and dose limiting toxicities (DLT).
Part 2: Groups A - E, and F: • Frequency and nature of AEs. • Overall response rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (CBR)
Part 2: Groups A - E, and F: • Frequency and nature of AEs. • Overall response rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (CBR)
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.
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.
次要结局
- 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.
- 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.
- 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.
研究者
Debasish Roychowdhury
Scientific
Partner Therapeutics Inc.
研究点 (18)
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