A Phase 1, Open-Label, Multicenter Study of INCA32459 in Participants With Select Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 13
- 主要终点
- Part 1: Occurrence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is a multicenter, open-label, single-arm study to investigate the safety, tolerability, PK, pharmacodynamics and preliminary activity of INCA32459 in participants with selected advanced malignancies. Part 1 (dose escalation) will determine the recommended dose of INCA 32459 for expansion (RDE) and the maximum tolerated dose (MTD). Part 2 (dose expansion) will further evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of INCA 32459 at the recommended dose(s) for expansion in 2 tumor-specific cohorts.
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
- •Histologically or cytologically confirmed advanced malignancies as follows:
- •Part 1 only: Participants with the select advanced malignancies as specified in the protocol.
- •Part 2 only:
- •Cohort 1 only: Participants with Stage III (unresectable) or Stage IV (metastatic) melanoma that is considered nonamenable to curative treatments or procedures.
- •Cohort 2 only: Participants with histologically or cytologically confirmed recurrent/metastatic SCCHN that is PD-L1 positive (CPS ≥ 1) which is not amenable to local therapy with curative intent.
- •Participants must have experienced disease progression after treatment with standard therapies, or are intolerant to or ineligible for standard treatment:
- •Part 1: All available standard therapies, including anti-PD-(L)1 and platinum-based therapy, if applicable, that are known to confer clinical benefit. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.
- •Part 2: Available standard therapies, including anti-PD-(L)1 and platinum-based therapy, if applicable, that are known to confer clinical benefit. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance. Part 2 participants may have received up to 2 prior systemic therapies in the a advanced/metastatic setting.
- •ECOG performance status of 0 or 1
- •Part 2 only: Measurable disease according to RECIST v1.
- •Part 2 only: Willingness to undergo a fresh tumor biopsy at screening (core or excisional).
- •Part 2 only: Willingness to undergo a fresh tumor biopsy at screening and on-treatment in selected participant.
- •Willingness to avoid pregnancy or fathering children
排除标准
- •Prior treatment with any LAG-3- or MHC Class II-directed therapy for current malignancy, or any prior malignancy.
- •Treatment with anticancer therapies or participation in another interventional clinical study within 28 days before the first administration of study treatment (this includes curative radiation to the thorax or systemic anticancer therapies).
- •Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy (with exceptions specified in the protocol).
- •Not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment.
- •Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment.
- •Any known additional malignancy that is progressing or requires active treatment; history of other malignancy within 3 years of the first dose of study treatment (with exceptions specified in the protocol).
- •Evidence of interstitial lung disease or history of interstitial lung disease, or active, noninfectious pneumonitis.
- •Active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
- •Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
- •Chronic treatment with systemic steroids (> 10 mg/day of prednisone or equivalent).
研究组 & 干预措施
Part 1: Dose Escalation
INCA32459 will be administered at a protocol defined starting regimen intravenously. Subsequent dose regimens will be determined during study conduct.
干预措施: INCA32459-101 (Drug)
Part 2: Dose Expansion Cohort Disease Group 1
INCA32459 will be administered at the recommended dose or doses for expansion (RDE[s]) for unresectable or metastatic melanoma.
干预措施: INCA32459-101 (Drug)
Part 2: Dose Expansion Cohort Disease Group 2
INCA32459 will be administered at the recommended dose or doses for expansion (RDE[s]) for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is PD-L1 positive.
干预措施: INCA32459-101 (Drug)
结局指标
主要结局
Part 1: Occurrence of Dose Limiting Toxicities (DLTs)
时间窗: Up to approximately 12 months
Toxicities occurring during Part 1 will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.
Number of Participants with Dose Interruptions due to TEAE
时间窗: Up to approximately 12 months
Dose interruptions will occur according to protocol guidelines.
Number of Participants discontinue study due to TEAE
时间窗: Up to approximately 12 months
TEAE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to approximately 12 months
TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
次要结局
- PK Parameters: AUC(Up to 24 months)
- PK Parameters: Vz(Up to 24 months)
- Objective Response Rate (ORR)(Up to 12 months)
- Disease Control Response (DCR)(Up to 12 months)
- PK parameters: Cmax(Up to 24 months)
- PK Parameters: CL(Up to 24 months)
- Duration of Response (DOR)(Up to 12 months)
- PK parameters: tmax(Up to 24 months)
- PK parameters: Cmin(Up to 24 months)
- PK Parameters: t1/2(Up to 24 months)
- Receptor Occupancy(Up to 24 months)