A Phase 2, Open-label, Multicenter Study Investigating Oncolytic Immunotherapy in Combination With Other Therapy in Patients With Locoregionally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 34
- 主要终点
- LA Cohort: Progression-free Survival
研究概览
简要总结
This is a Phase 2, multicenter, open-label, 2-cohort (Locoregionally Advanced Cohort or Recurrent/Metastatic Cohort) study evaluating RP3 in combination with concurrent chemoradiation therapy (CCRT) followed by nivolumab (for the LA Cohort) or combined with chemotherapy and nivolumab (for the R/M Cohort) in patients with advanced, inoperable squamous cell carcinomas of the head and neck (SCCHN), including of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary.
详细描述
RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly kill tumor cells and generate a systemic anti-tumor immune response
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx or of a lymph node(s) anywhere in levels I to V of the neck that has been excluded clinically from association with cancer from a non-head and neck site
- •All patients Must be willing to consent to provide archival or fresh tumor biopsy samples obtained within 60 days prior to initiation of study treatment. Patients must also consent to provide on-treatment biopsies as per protocol.
- •At least 1 measurable lesion of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes), in accordance with RECIST.
- •At least injectable tumors of at least 1 cm in aggregate overall longest diameter.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 -
- •Locally Advanced Cohort Only
- •patients must not be amenable to surgery with curative intent
- •Previously untreated high-risk disease meeting at least 1 of the following criteria:
- •Oral cavity, hypopharynx, larynx, oropharynx (p16 negative): Stage III/ IV Note: Cancers of the oral cavity, hypopharynx, and larynx are eligible irrespective of p16 status. These patients will not be stratified by p16 status.
- •For p16 positive oropharynx cancers, patients must have either
- •T3 and/or N2 or greater disease with active smoking and/or greater than 20 pack year smoking history OR
- •T4 and/or N3 disease irrespective of tobacco use
- •SCCHN of unknown primary Stage III/IV irrespective of p16 status or smoking status.
- •Eligible for definitive CCRT with curative intent.
- •R/M Cohort Only
- •Has recurrent or metastatic SCCHN eligible for first line systemic therapy for R/M disease.
- •Has a PD-L1 CPS <20.
排除标准
- •Primary tumors of nasopharynx, paranasal sinuses, nasal passages, salivary gland, thyroid or parathyroid gland, or skin.
- •Tumors with histopathology indicating the tumor has sarcomatous, sarcomatoid, verrucous, mixed, undifferentiated, or otherwise nonsquamous components.
- •Has an airway that is not deemed safe and stable on flexible fiberoptic laryngoscopy (FFL) performed by a head & neck cancer specialist within 7 days of first RP3 injection.
- •Has a baseline serum albumin (at Screening) <2.5 g/dL and/or evidence of cachexia or muscle wasting during physical exam at Screening.
- •Known acute or chronic hepatitis B or acute or chronic hepatitis C
- •Systemic infection requiring intravenous (IV) antibiotics
- •Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis)
- •History of interstitial lung disease.
- •History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
- •Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
- •Administration of live vaccine within 28 days prior to the first dose of study treatment.
- •History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment.
- •History of life-threatening toxicity related to prior immune treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- •History of viral infections according to the protocol
- •Treatment with botanical preparations within 2 weeks prior to treatment.
- •Major surgery ≤ 2 weeks prior to starting study treatment.
- •LA Cohort only
- •Has received prior radiotherapy for SCCHN.
- •Has received any prior systemic therapy for SCCHN.
- •R/M cohort only
- •Is eligible for radiation and/or surgery with curative intent.
- •Has received systemic therapy for recurrence or new (ie, not present at the time of initial diagnosis) metastases of SCCHN.
- •Received a paclitaxel-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of stable disease (SD) or PD (patients who achieved a partial response [PR] or CR are eligible).
- •Received a carboplatin-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of SD or PD (patients who achieved PR or CR are eligible).
- •Patients with known intolerance to carbo-platinum and/or paclitaxel, including hypersensitivity to Cremophor® EL (polyoxyethylated castor oil).
- •Previously received multiple courses of irradiation to the same anatomic site unless such patient has nondoubly-irradiated, measurable, injectable lesions, which are the only lesions to be used as target lesions (for nodal disease, only lesions in nodal basins that have been previously irradiated just once or not irradiated at all may be injected and/or used as target lesions).
- •Note: Other protocol defined inclusion/exclusion criteria apply for each cohort
研究组 & 干预措施
LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: RP3 (Biological)
LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: CCRT(concurrent chemoradiation therapy) (Other)
LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: nivolumab (Biological)
LA Cohort: concurrent chemoradiation therapy in Patients With Locoregionally Advanced SCCHN
standard-of-care CCRT (defined as intensity-modulated radiation therapy [IMRT] and cisplatin
干预措施: CCRT(concurrent chemoradiation therapy) (Other)
R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: RP3 (Biological)
R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: carboplatin and paclitaxel (Other)
R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN
RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.
干预措施: nivolumab (Biological)
结局指标
主要结局
LA Cohort: Progression-free Survival
时间窗: From Day 1 to documented progression of disease (up to 3 years)
Progression-free survival is defined as the time from the first day of study treatment to the date of progression of disease, which was subsequently confirmed, or death by any cause, whichever occurs first
R/M Cohort: Objective Response Rate
时间窗: From Day 1 to documented progression of disease (up to 3 years)
Percentage of subjects achieving objective response (complete response + partial response)
次要结局
- LA Cohort: Proportion of Patients Achieving No-Evidence-of-Disease Status by Any Means (Including Salvage Surgery)(From Day 1 to end of study (up to 3 years))
- LA Cohort: Summary of Patient-Reported Outcomes Measured by EQ-5D-5L(From Day 1 to 52 Weeks)
- R/M Cohort: Progression-free Survival(From Day 1 to documented progression of disease (up to 3 years))
- LA Cohort: Summary of Patient-Reported Outcomes Measured by FACT-HNSI-22(From Day 1 to 52 Weeks.)
- R/M Cohort: Progression-free Survival Rates at 6 and 12 Months(From Day 1 to documented progression of disease (up to 12 months))
- R/M Cohort: Duration of Response(From Day 1 to documented progression of disease (up to 3 years))
- R/M Cohort: Duration of Clinical Benefit(From Day 1 to documented progression of disease (up to 3 years))
- R/M Cohort: Disease Control Rate(From Day 1 to documented progression of disease (up to 3 years))
- LA Cohort: Overall Survival Rate at 1, 2, and 3 Years(From Day 1 to date of death by any cause (up to 3 years))
- LA Cohort: Cumulative Incidence of Distant Metastatic Failure(From Day 1 to end of study (up to 3 years))
- LA Cohort: Duration of Clinical Benefit(From Day 1 to documented progression of disease (up to 3 years))
- LA Cohort: Frequency, Nature, and Severity of TEAEs and SAEs(From Screening through 60 days after last dose of RP3, or 100 days after last dose of nivolumab, or 28 days after last dose of either cisplatin, carboplatin, or paclitaxel, whichever occurs last)
- LA Cohort: Progression-free Survival Rates at 6 and 12 Months(From Day 1 to documented progression of disease (up to 12 months))
- LA Cohort: Overall Response Rate and Metabolic Overall Response Rate(From Day 1 to documented progression of disease (up to 3 years))
- LA Cohort: Cumulative Incidence of Locoregional Failure(From Day 1 to end of study (up to 3 years))
- LA Cohort: Complete Response Rate and Metabolic Complete Response Rate at 5-and 8-months Following of Initiation of Radiation Following of Initiation of Radiation(From Day 1 to documented progression of disease (up to 8Months Following of Initiation of Radiation))
- R/M Cohort: Overall Survival Rates at 1, 2, and 3 Years(From Day 1 to date of death by any cause (up to 3 years))
- R/M Cohort: Complete Response Rate(From Day 1 to documented progression of disease (up to 3 years))
- R/M Cohort: Frequency, Nature, and Severity of TEAEs and SAEs(From Screening through 60 days after last dose of RP3, or 100 days after last dose of nivolumab, or 28 days after last dose of either cisplatin, carboplatin, or paclitaxel, whichever occurs last)
- R/M Cohort: Number of Patients Who Undergo Attempted Definitive Resection(From Day 1 to end of study (up to 3 years))