A Phase II, Multi-site, Randomized, Open-label, Trial of Pumitamig in Combination With Chemotherapy in Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- BioNTech SE
- 入组人数
- 105
- 试验地点
- 24
- 主要终点
- Confirmed overall response rate
研究概览
简要总结
This study will enroll adults with confirmed metastatic pancreatic ductal adenocarcinoma (PDAC, systemic PDAC treatment naïve), Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function. Participants will receive pumitamig (also known as BNT327, BMS-986545, or PM8002) in combination with chemotherapy.
详细描述
Participants will be assigned to treatment arms with modified (m) FOLFIRINOX administration (Treatment Arms 1 and 2) or the treatment arm with nab-paclitaxel + gemcitabine administration (Treatment Arm 3) based on the physician's choice of chemotherapy. Study participants assigned to arms with mFOLFIRINOX administration, will be randomized 1:1 to one of the two arms (Treatment Arms 1 or 2). Once enrollment of Treatment Arms 1 to 3 has been completed, enrollment into the exploratory cohorts (Treatment Arms 4A and 4B) will be opened.
There will be a screening period of up to 28 days, followed by a treatment period lasting up to 2 years. After administration of the last dose of study treatment, participants will be followed-up for safety for up to 90 days or until the participant initiates new anticancer treatment (e.g., systemic, radiotherapy/surgery). Thereafter, survival follow-up will be conducted until the participant dies or withdraws consent for survival status follow-up, loss of contact, or study termination (whichever occurs first).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Have a histologically or cytologically confirmed metastatic PDAC. A tissue sample, archival or fresh, must be provided during the screening period, unless biopsy is not feasible due to safety concerns.
- •Have not received prior systemic therapy for unresectable metastatic PDAC. For participants who have received prior induction chemotherapy, concurrent chemoradiotherapy, or adjuvant/neoadjuvant chemotherapy for curative-intent, the interval should be at least 6 months from the end of the last treatment to relapse.
- •Have at least one measurable lesion as the targeted lesion based on RECIST v1.
- •Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures) are not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system [CNS] metastasis should not be considered as a measurable lesion).
- •Agree to discontinue strong inhibitors or inducers of cytochrome P450 enzyme (CYP3A), CYP2C8, glucuronosyltransferase 1 family, polypeptide A cluster 1A (UGT1A1) at least 2 weeks prior to starting study treatment, and change to other treatment regimens at screening if such drugs are used.
排除标准
- •Have received any of the following therapies or drugs before study enrollment:
- •Have received prior systemic anticancer therapy for unresectable metastasis disease. Prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment
- •Any immunostimulatory, or immunosuppressive treatment within 4 weeks (or five half-lives, whichever is longer) before starting study treatment.
- •PD(L)-1/VEGF bispecific antibody, including monotherapy with either category or combinations thereof.
- •Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 days before starting study treatment. Exception: Excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergies) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
- •Vaccinations with live attenuated vaccine(s) within 4 weeks before starting study treatment.
- •Any non-study investigational medicinal product within five half-lives of the first dose or within 4 weeks, whichever is longer, before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
- •Have undergone major organ surgery (core needle biopsies are allowed >7 days before starting study treatment), open biopsy, significant trauma, or invasive dental procedures (such as dental implants) within 28 days before starting study treatment, or a planned/anticipated need for major surgery during the study treatment period. Placement of vascular infusion devices is allowed. Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications from the treatment before starting study treatment.
- •Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
- •Have spinal cord compression or CNS metastases that are untreated and symptomatic or require treatment with corticosteroids or anticonvulsants for associated-symptom control. Exception: Treated brain metastases which are no longer symptomatic and for which no corticosteroid or anticonvulsant treatment is needed (the participant must have recovered from the acute toxic effect of radiotherapy).
- •Have active autoimmune disease or history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes mellitus.
- •Have had other malignant tumors within 5 years before starting study treatment. Exception: Those who have been cured with local treatment (such as basal cell or squamous-cell carcinoma of the skin, superficial or noninvasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, and papillary carcinoma of thyroid and early-stage prostate cancer).
- •Have heart conditions as specified in the protocol within 6 months before starting study treatment.
- •History of myocardial infarction, unstable angina, arterial thrombosis or cerebrovascular accident within 6 months before starting study treatment.
- •History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism within 3 months prior to randomization, unless the participant has been fully treated (e.g., inferior vena cava filter placed) and/or adequately anticoagulated on a prophylactic dose.
- •Have serious or non-healing wounds, ulcers, or (incompletely healed) bone fractures. This includes history (within 6 months before starting the study treatment) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
- •Have significant risk of hemorrhage (in the opinion of the investigator) or evidence of major coagulation disorders as specified in the protocol.
- •Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Those with indwelling catheters (e.g., PleurX) are allowed.
- •Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade 3 or higher irAEs that did not lead to treatment discontinuation of a prior immunotherapy may be enrolled at the investigator's discretion.
- •Have adverse events (AEs) from prior antitumor therapy that have not returned to Grade 1 (graded by CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, or stable hypothyroidism under hormone replacement therapy).
- •Have gastrointestinal symptoms or conditions as specified in the protocol.
- •Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
- •Have superior vena cava syndrome or symptoms of spinal cord compression.
- •Have active, or a history of, pneumonitis requiring treatment with steroids, or have active or a history of interstitial lung disease. Those with a history of pulmonary fibrosis or with currently diagnosed severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiotherapy, chemotherapy, or other factors such as smoking are allowed.
- •Have active infection (e.g., bacterial or fungal infections or tuberculosis) requiring systemic treatment or any uncontrolled infection within 14 days prior to the first dose of study treatment.
- •Have active syphilis. Participants with inactive previous infection could be eligible: Infection with a positive non-specific antibody test for syphilis (e.g., TRUST [Toluidine Red Unheated Serum Test], Rapid Plasma Reagin [RPR], TP-PA [Treponema pallidum Particle Agglutination]) or have a positive syphilis-specific antibody test (e.g., TPPA) (a positive "syphilis-specific antibody test" but a negative "non-specific antibody test for syphilis" for more than 1 year) infection.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Pumitamig (Drug)
Arm 4B (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen
干预措施: Pumitamig (Drug)
Arm 4B (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen
干预措施: mFOLFIRINOX (Drug)
Arm 2: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: mFOLFIRINOX (Drug)
Arm 2: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Pumitamig (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Pumitamig (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Gemcitabine (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Nab-paclitaxel (Drug)
Arm 1: Pumitamig (dose level 1) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: mFOLFIRINOX (Drug)
Arm 1: Pumitamig (dose level 1) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
干预措施: Pumitamig (Drug)
结局指标
主要结局
Confirmed overall response rate
时间窗: Up to 24 months
For each treatment arm. Defined as the percentage of study participants in whom a confirmed complete response (CR) or confirmed partial response (PR) (assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response.
Occurrence of treatment emergent adverse events (TEAEs) by severity
时间窗: From the first dose of study treatment until 90 days after the last dose of study treatment (up to 32 months).
According to (US National Cancer Institute) Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v5.0\]). By relationship and for each treatment arm.
Occurrence of dose interruptions, reductions, and discontinuations due to TEAEs
时间窗: Up to 24 months after first dose
For each treatment arm.
次要结局
- Disease control rate(Up to 24 months)
- Duration of response(Up to 30 months)
- Progression free survival(Up to 32 months)
- Overall survival(Up to 32 months)
- Pharmacokinetic (PK) assessment: Maximum concentration (Cmax) derived from serum concentration of pumitamig(Up to 6 months from first dose of study treatment)
- PK assessment: Minimum concentration (Cmin) derived from serum concentration of pumitamig(Up to 6 months from first dose of study treatment)
- Incidence of detectable pumitamig anti-drug antibodies in serum(Up to 32 months)