Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Genmab
- 入组人数
- 884
- 试验地点
- 116
- 主要终点
- Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
研究概览
简要总结
This study will test the safety, including side effects, and determine the characteristics of a drug called Rina-S in participants with solid tumors.
Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).
详细描述
This is a Phase 1/2 study of Rina-S; also known as GEN1184, formerly known as PRO1184, a folate receptor alpha (FRα) targeted antibody-drug conjugate, to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of Rina-S in participants with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma.
The study consists of multiple parts:
Part A: monotherapy cohorts
Part B: tumor-specific monotherapy dose-expansion cohorts
Part C: platinum-resistant ovarian cancer (PROC) monotherapy cohort
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
- •Part A and B:
- •Histologically or cytologically confirmed metastatic or unresectable solid malignancy including ovarian cancer (must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer), endometrial cancer, non-small cell lung cancer (Part A), EGFR-mutated NSCLC (Part B), breast cancer (hormone receptor positive, HER2-negative and triple-negative) (Part A), mesothelioma or cervical cancer (Part B).
- •Previously received therapies known to confer clinical benefit.
- •Measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline.
- •Part C, E, and H:
- •Participants must have histologically or cytologically confirmed metastatic or unresectable epithelial ovarian cancer as specified below.
- •High grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding endometrioid, clear cell carcinomas, mucinous, low grade, and those with a sarcomatous or neuroendocrine element)
- •Participants must have received up to 3 prior lines of therapy. Participants may have had up to to 4 prior lines of therapy are allowed if MIRV is locally approved and was used as the last line of therapy. Participants must have progressed radiographically on or after their most recent line of therapy.
- •Participants must have platinum-resistant ovarian cancer.
- •Participants must have received prior bevacizumab or approved biosimilar.
- •Participants with known or suspected deleterious germline or somatic BRCA mutations (as determined by Food and Drug Administration [FDA]-approved test in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory; or locally approved equivalent) and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment.
- •Measurable disease per the RECIST v1.1 at baseline.
- •Participants must have platinum-sensitive ovarian cancer.
- •Participants must have received 1 to 3 prior lines of therapy.
- •Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
- •Participants with primary platinum-refractory ovarian cancer must have received ≤2 prior lines of therapy. Primary platinum-refractory ovarian cancer is defined as a lack of response or by progression within 91 days after completing front-line platinum containing therapy.
- •Participants must have received 1 to 3 prior lines of therapy for platinum-resistant ovarian cancer (PROC), and up to 4 prior lines of therapy for platinum-sensitive ovarian cancer (PSOC). Prior treatments may have included bevacizumab, PARP inhibitor, and MIRV.
- •Participants with PSOC must have disease progression on or after maintenance treatment, or at least 6 months (>183 days) or more from the last dose of platinum-based therapy.
- •Endometrial cancer (any subtype excluding sarcoma).
- •Primary advanced or recurrent endometrial cancer (any subtype excluding sarcoma and neuroendocrine tumors).
- •Part F and G:
- •Participants must have histologically or cytologically confirmed EC.
- •Recurrent progressive EC (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma) following prior therapy.
- •Participants must have received 1 to 3 prior lines of therapy, and must have progressed radiographically on or after their most recent line of therapy:
- •Participants must have received prior platinum-based chemotherapy and a programmed death-ligand 1 (PD-[L])1 inhibitor.
- •Participants who progress >12 months after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy must receive 1 additional cytotoxic systemic treatment prior to enrollment in this study.
- •Hormonal therapy alone (i.e., without chemotherapy) will not be counted as a separate line of therapy.
- •Measurable disease per the RECIST Version 1.1 at baseline.
- •Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer (excluding clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies or low grade/borderline ovarian tumors).
- •Participants must have platinum sensitive ovarian cancer.
- •Measurable disease per the RECIST Version 1.1 at baseline.
- •Participants must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding mucinous, low grade, and those with a sarcomatous or neuroendocrine element.
- •Measurable disease per the RECIST Version 1.1 at baseline.
- •Participants must have histologically or cytologically confirmed metastatic or unresectable ovarian cancer (must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding mucinous, low grade, and those with a sarcomatous or neuroendocrine element).
- •Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
- •Measurable disease per the RECIST Version 1.1 at baseline.
排除标准
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids within the past 2 years, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate.
- •Note: Other protocol-defined inclusion/exclusion may apply.
研究组 & 干预措施
Part A, B, C, E, F, G, H, I, J and K
Rina-S monotherapy in Part A and at the recommended dose in Parts B, C, E, F, G, H, I, J and K.
干预措施: Rina-S (Drug)
Part D1
Rina-S in combination with carboplatin
干预措施: Rina-S (Drug)
Part D1
Rina-S in combination with carboplatin
干预措施: Carboplatin (Drug)
Part D2 and I
Rina-S in combination with bevacizumab
干预措施: Rina-S (Drug)
Part D2 and I
Rina-S in combination with bevacizumab
干预措施: Bevacizumab (Drug)
Part D3 and D4
Rina-S in combination with pembrolizumab
干预措施: Pembrolizumab (Drug)
Part D3 and D4
Rina-S in combination with pembrolizumab
干预措施: Rina-S (Drug)
结局指标
主要结局
Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
时间窗: Through end of treatment, up to approximately 1 year.
Parts A, and D - Dose Limiting Toxicity (DLT)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
The proportion of participants experiencing DLT.
Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter
时间窗: Cycles 1 to 3 (each cycle is 21 days)
Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
时间窗: Through end of treatment, up to approximately 1 year.
Parts A, and D - Dose Limiting Toxicity (DLT)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
The proportion of participants experiencing DLT.
Parts C, F, G, H, I, and J- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR, Parts C, E, and F) or Investigator (Part G, I, and J) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: Through end of treatment, up to approximately 1 year.
Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.
Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter
时间窗: Cycles 1 to 3 (each cycle is 21 days)
次要结局
- Parts A, B, and D - Best Overall Response (BOR)(Up to approximately 1 year.)
- Parts A, B, and D - Disease Control Rate (DCR)(Up to approximately 1 year.)
- Parts A, B, and D - Best Overall Response (BOR)(Up to approximately 1 year.)
- Parts A, B, and D - ORR(Up to approximately 1 year.)
- Parts A, B, and D - Disease Control Rate (DCR)(Up to approximately 1 year.)
- Parts A, B, C, D, F, G, H, I, and J - Progression-Free Survival (PFS)(Through end of treatment, up to approximately 1 year.)
- Parts C, F, G, H, I and J - Overall survival (OS)(Up to approximately 2 years.)
- Parts A, B, C, D, F, H, I and J - Duration of Objective Response (DOR)(From date of enrollment until the date of first documented disease progression or date of study withdrawal, whichever came first, assessed up to 12 months.)
- Parts A, B, and D - Peak Plasma Concentration (Cmax) for Rina-S(Through end of treatment, up to approximately 1 year.)
- Parts A, B, and D - Area Under the Plasma Concentration Versus Time Curve (AUC) for Rina-S(Through end of treatment, up to approximately 1 year.)
- Parts A, B, and D -Time to Reach Cmax (Tmax) for Rina-S(Through end of treatment, up to approximately 1 year)
- Parts A, B, and D - Trough Concentrations (Ctrough) for Rina-S(Through end of treatment, up to approximately 1 year)
- Parts A, B, and D - Apparent Terminal Half-life (t1/2) for Rina-S(Through end of treatment, up to approximately 1 year)
- Parts C, D, H and J - CA-125 Response Determined Using the Gynecologic Cancer Intergroup (GCIG) Criteria(Through end of treatment, up to approximately 1 year)
- Parts C, F, H, I, J, and K - Number of Participants with Type, Incidence, Severity, Seriousness as per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and Relatedness of Adverse Events (AEs)(Through end of treatment, up to approximately 1 year)