NCT05592626招募中1 期
A Phase 1/2, First-in-Human, Open-Label, Dose Escalation and Expansion Study of STAR0602, a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule, in Subjects With Unresectable, Locally Advanced, or Metastatic Solid Tumors That Are Antigen-rich (START-001)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 366
- 试验地点
- 49
- 主要终点
- Phase 1 (Dose Escalation):Number of Participants with Dose-limiting Toxicities (DLTs) in Cycle 1
研究概览
简要总结
This is an open label, multicenter, phase 1/2 study to assess the safety/tolerability and preliminary clinical activity of STAR0602 as a single agent and in combination with chemotherapy administered intravenously in participants with advanced solid tumors that are antigen-rich.
详细描述
This Phase 1/2 study consists of two parts: Phase 1 Dose Escalation and Phase 2 Dose Expansion. In Phase 1 Dose Escalation, STAR0602 will be administered intravenously in participants with advanced solid tumors to assess safety/tolerability profile of STAR0602 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of STAR0602. In Phase 2 Dose Expansion, STAR0602 at RP2D will be administered to participants with advanced, antigen-rich solid tumors to further evaluate safety and assess preliminary clinical activity of STAR0602. Clinical activity will be evaluated by objective tumor response rate (ORR), duration of response (DOR), disease control rate (DCR), and progression free survival (PFS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically confirmed solid tumors that are unresectable, locally advanced, or metastatic and for which standard curative therapies do not exist or are no longer effective or have intolerable toxicities. Participants should not have received more than three regimens of prior therapies for their advanced or metastatic diseases. For Phase 2 Cohorts 8 and 10 (see below), participants should not have received more than one line of prior therapy.
- •For Phase 1, participants must have one of the following solid tumors:
- •High mutational burden (TMB-H)
- •Microsatellite Instability (MSI-H)/DNA mismatch repair (dMMR)
- •Virally associated tumors
- •Solid tumors generally considered as immunogenic (e.g., melanoma and renal cell carcinoma) are eligible without prior testing for TMB, MSI or viral status after the Sponsor's approval.
- •For Phase 2, participants must have one of the following solid tumors:
- •TMB-H (not enrolling)
- •MSI-H/dMMR (not enrolling)
- •CRC (both Ras wild type and mutant) (not enrolling)
- •NSCLC (recurrent or Primary Stage 4)
- •CRC with pMMR/MSS (without TMB-H requirement)
- •(Other tumor histologies may also be included in Phase 2 as additional data emerge to support their inclusion.)
- •Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment:
- •No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids > 10 mg prednisone/day or equivalent);
- •No concurrent leptomeningeal disease or cord compression.
- •Subjects who have previously received a CPI (e.g., anti-PD-L1, anti-PD-1, anti CTLA 4) prior to enrollment must have CPI immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the CPI) to be eligible for enrollment.
- •Subjects who experienced previous CPI-related endocrine abnormalities are eligible for the study regardless of CTCAE grade if well controlled on replacement therapy.
- •Subjects who have had previous CPI-related Grade 3 to 4 pneumonitis, peri/myocarditis, colitis and bowel perforation, myositis, encephalitis, or peripheral neuropathy will need Sponsor approval.
排除标准
- •Participants with a history of known autoimmune disease with exceptions of:
- •Vitiligo;
- •Psoriasis, atopic dermatitis or other autoimmune skin condition not requiring systemic treatment;
- •History of Graves' disease, now euthyroid for > 4 weeks;
- •Hypothyroidism managed by thyroid replacement;
- •Alopecia;
- •Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs.
- •Adrenal insufficiency well controlled on replacement therapy.
- •Major surgery or traumatic injury within 8 weeks before first dose of study drug.
- •Unhealed wounds from surgery or injury.
- •Treatment with >10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within 7 days prior to the initiation of study drug. Exceptions may be made for patients who have had allergic reaction to iodinated contrast media. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed.
- •Prior therapy within the following timeframe before planned infusion of STAR0602 as follows:
- •Cytotoxic chemotherapy, small molecule inhibitors, radiation, interventional radiology procedure, or similar investigational therapies within ≤ 2 weeks or participants who have not recovered (i.e., ≤ Grade 1 or to baseline) from AEs due to a previously administered agent;
- •Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar investigational therapies within 6 weeks prior to the initiation of study drug or participants who have not recovered (i.e., ≤ Grade 1 or to baseline) from AEs due to agents administered more than 4 weeks earlier. Note: Participants with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
- •Clinically significant cardiovascular/vascular disease, gastrointestinal disorders, inflammatory processes, pulmonary compromises
- •Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
- •Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
- •Participants who are known to be human immunodeficiency virus positive or hepatitis B or C positive and have uncontrolled disease.
- •Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required systemic therapy, with the exception of indolent lymphomas.
- •Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation).
- •Hepatic metastases unless adequately treated, either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically or both, and stable for 3 months.
- •Bulky disease defined as any lesion ≥ 5 cm in greatest dimension unless approved by the Sponsor.
研究组 & 干预措施
Phase 1: Advanced Solid Tumors
Experimental
Dose Escalation; Intervention: Drug: STAR0602, Invikafusp alfa
干预措施: STAR0602 (Drug)
Phase 2: Advanced Solid Tumors
Experimental
Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602, Invikafusp alfa
干预措施: STAR0602 (Drug)
Phase 2: Advanced Solid Tumors
Experimental
Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602, Invikafusp alfa
干预措施: Docetaxel (Taxotere) (Combination Product)
Phase 2: Advanced Solid Tumors
Experimental
Dose Expansion; Recommended Phase 2 Dose (RP2D) identified from Phase 1 will be used in Phase 2; Intervention: Drug: STAR0602, Invikafusp alfa
干预措施: Irinotecan (Camptosar) (Combination Product)
结局指标
主要结局
Phase 1 (Dose Escalation):Number of Participants with Dose-limiting Toxicities (DLTs) in Cycle 1
时间窗: Cycle 1 (Cycle length= 28 days)
Phase 1 and 2 (Dose Escalation and Expansion): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 3 years
Phase 2 (Dose Expansion): Percentage of Participants with Overall Objective Tumor Responses (ORR)
时间窗: Up to 3 years
Complete response (CR) and partial response (PR)
次要结局
- Phase 2 (Dose Expansion): Progression Free Survival (PFS)(Up to 3 years)
- Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with ORR(Up to 3 years)
- Phase 1 and 2 (Dose Escalation and Expansion): Duration of Responses (DOR)(Up to 3 years)
- Phase 1 and 2 (Dose Escalation and Expansion): Percentage of Participants with Disease Control (CR, PR, and Stable Disease)(Up to 3 years)
- Phase 2 (Dose Expansion): Overall Survival (OS)(Up to 3 years)
- Phase 1 and 2 (Dose Escalation and Expansion): Maximum Observed Plasma Concentration (Cmax) for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Anti-drug Antibody (ADA) formation(Dose Escalation and Expansion: Day 1 of predetermined cycles up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Time (Tmax) to Reach the Maximum Plasma Concentration (Cmax) for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration (AUC) Versus Time Curve for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Terminal Elimination Half-life (t1/2) for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Apparent Volume of Distribution (Vd) for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
- Phase 1 and 2 (Dose Escalation and Expansion): Apparent Total Body Clearance (CL) for STAR0602(Dose Escalation: Cycle 1 and Cycle 6 at predefined intervals up to 1 year; Dose Expansion: Cycle 1, Cycle 3, and Cycle 6 at predefined intervals up to 3 years (Cycle length= 28 days))
研究者
研究点 (49)
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相关资讯
Marengo Therapeutics Completes Enrollment in Phase 1/2 STARt-001 Monotherapy Cohorts for Invikafusp Alfa in PD-1–Resistant Solid Tumors- Marengo Therapeutics has completed enrollment in the monotherapy cohorts of its Phase 1/2 STARt-001 trial evaluating invikafusp alfa in PD-1–resistant, antigen-rich solid tumors.
- Updated STARt-001 results have been selected for an oral presentation at the ESMO 2026 Congress, taking place October 23–27 in Madrid, Spain.
- The company appointed Amy Otto as SVP of Program Leadership and Zhenming Shun, Ph.D., as SVP of Data Science to support late-stage development.
- Following ESMO and planned FDA interactions, the next stage of invikafusp alfa development is expected to begin in 2027.10 days agoMarengo Secures ESMO 2026 Oral Presentation for Phase 2 Invikafusp Alfa Data in PD-1–Resistant Solid Tumors, Appoints KEYTRUDA Development Leader Eric Rubin to Scientific Advisory Board- Marengo Therapeutics' Phase 2 data for invikafusp alfa, a first-in-class bispecific dual T-cell agonist, has been selected for an oral presentation at ESMO Congress 2026.
- The STARt-001 trial evaluates invikafusp alfa monotherapy in biomarker-enriched cohorts of patients with TMB-H solid tumors resistant to PD-1–directed therapy.
- Eric Rubin, M.D., former Merck SVP who led pembrolizumab (KEYTRUDA®) initial development, has joined Marengo's Scientific Advisory Board to guide the next development phase.
- Invikafusp alfa selectively activates Vβ6/Vβ10 T-cell subsets via combined non-clonal TCR activation and IL-2 signaling, aiming for durable antitumor immunity with limited systemic immune activation.2 months agoFDA Grants Fast Track Designation to Invikafusp Alfa for Advanced Colorectal Cancer- The FDA granted Fast Track designation to invikafusp alfa (STAR0602) for advanced colorectal cancer with high tumor mutational burden (TMB-H).
- Phase 1 data showed invikafusp alfa yielded a 50% disease control rate and tumor shrinkage in 32% of patients across six tumor types.
- The Phase 2 clinical trial is ongoing, evaluating invikafusp alfa monotherapy in PD-1 resistant tumors across multiple sites in Europe.
- Invikafusp alfa selectively targets Vβ T cells, offering a novel approach for PD-1 insensitive or resistant tumors like colorectal cancer.last yearMarengo's Invikafusp Alfa Shows Promise in Anti-PD-1 Resistant Cancers- Marengo Therapeutics' invikafusp alfa (STAR0602) demonstrates tumor shrinkage in heavily pre-treated, anti-PD-1 resistant patients across multiple tumor types.
- The STARt-001 Phase 1 trial highlights invikafusp alfa's manageable safety profile and clinical activity, particularly in cancers with high tumor mutation burden (TMB-H).
- Invikafusp alfa achieves sustained in vivo expansion of TCRVβ6/Vβ10 T cells, with disease control observed in 50% of patients in dose escalation cohorts.
- Recommended Phase 2 dose (RP2D) of 0.08 mg/kg was selected for Phase 2 dose expansion studies based on safety, PK/PD data and preliminary anti-tumor activity.last yearMarengo's Invikafusp Alfa Shows Promise in Anti-PD-1 Resistant Solid Tumors- Marengo Therapeutics' invikafusp alfa (STAR0602) demonstrates tumor shrinkage across multiple tumor types in heavily pre-treated, anti-PD-1 resistant patients.
- The Phase 1 STARt-001 trial shows a manageable safety profile for invikafusp alfa, supporting its potential in high tumor mutational burden cancers.
- Invikafusp alfa achieves sustained and selective in vivo expansion of TCRVβ6/Vβ10 T cells, with disease control observed in 50% of patients.
- The recommended Phase 2 dose (0.08 mg/kg) was selected based on safety, PK/PD data, and preliminary anti-tumor activity, with Phase 2 expansion underway.last year