A Phase I, Open-label, Multi-arm, Multi-centre, Multi-dose, Dose Escalation Study of LTX-315 as Monotherapy or in Combination With Either Ipilimumab or Pembrolizumab in Patients With Transdermally Accessible Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 14
- 主要终点
- Dose limiting toxicity
研究概览
简要总结
The study will assess the safety, tolerability, PK and efficacy of different intra-tumoral dosing regimens of LTX-315; a lytic-peptide that induces long-term anti-cancer immune responses, as monotherapy or in combination with ipilimumab or pembrolizumab.
详细描述
In this phase I, open-label, multi-arm, multicentre, multi-dose dose escalation study in patients with transdermally accessible tumours; the safety, PK and efficacy of different dosing regimens of LTX-315 will be assessed.
Patients will be allocated into 4 separate (parallel) arms depending on the tumour type and the number of lesions available.
Arm A: Single lesion/sequential lesion treatment arm (LTX-315 monotherapy) (Completed) Arm B: Concurrent multiple lesion treatment arm with all tumour types (LTX-315 monotherapy) Arm C: LTX-315 combination with ipilimumab in patients with melanoma Arm D: LTX-315 combination with pembrolizumab in patients with TNBC
All patients will have at least one lesion available for injection.
Treatment schedule:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Arm A: (Recruitment completed)
- •Unresectable metastatic disease (any tumor type) and conventional anti-tumor treatment is not appropriate.
- •Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection between 1-3 cm longest diameter and one bystander lesion (non-injected).
- •Have unresectable/metastatic diagnosis of malignant melanoma (histologically confirmed).
- •Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection and biopsy which is between 1 and 3 cm in longest diameter.
- •Have had previous treatment with an anti-PD-1 antibody (as monotherapy or as part of combination (any combination) as 1st or 2nd line metastatic treatment).
- •Have unresectable/metastatic diagnosis of triple negative breast cancer (histologically confirmed).
- •Have at least one available lesion (cutaneous, sub-cutaneous or lymph node) for injection and biopsy with a minimum longest diameter of 1 cm.
- •Have received between one and 4 prior systemic treatments for metastatic triple negative breast cancer.
- •Be willing to undergo repeat tumour biopsy and/or tumour resection procedures.
- •Have an ECOG Performance status (PS): 0 -
- •Meet the following laboratory requirements:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •Absolute lymphocyte count ≥ 0.8 x 109/L
- •Platelet count ≥ 75 x 109/L
- •Haemoglobin ≥ 9.0 g/dL
- •aPTT/PT within the institution's normal range
- •Total bilirubin level ≤ 1.5 x ULN
- •ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis present)
- •Creatinine ≤ 1.5 x ULN
- •Albumin ≥ 30 g/L
排除标准
- •Arm A: (Completed)
- •Have a history of systemic auto-immune disease requiring anti-inflammatory or immunosuppressive therapy within the last 3 months. Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy and disease has been stable for ≥ 1 year.
- •Have had prior therapy with ipilimumab or any other anti-CTLA-4 monoclonal antibody.
- •Have had BRAF/MEK inhibitors administered within 2 weeks prior to the study drug administration.
- •Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; have a history of severe immune-related adverse reaction from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.
- •Have had prior therapy with an anti-PD-1 or anti-PD-L1 monoclonal antibody.
- •Have received cancer immunotherapy within 2 weeks prior to study drug administration or have not recovered from adverse events (to ≤ CTCAE grade 1) due to such agents.
- •Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; and have a history of severe immune-related adverse reactions from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.
- •Have received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to study drug administration, or have not recovered from adverse events (≤ CTCAE grade 1) due to agents administered more than 4 weeks earlier. Palliative radiotherapy to non-target lesions within 4 weeks prior to study drug administration is allowed.
- •Are currently taking any agent with a known effect on the immune system. Patients are allowed to be on a stable dose of corticosteroids (up to 10 mg daily prednisolone or equivalent) for at least 2 weeks prior to study drug administration (please see Appendix IV for prohibited medications).
- •Have any other serious illness or medical condition such as, but not limited to:
- •Uncontrolled infection or infection requiring antibiotics
- •Uncontrolled cardiac failure: Classification III or IV (New York Heart Association)
- •Uncontrolled systemic and gastro-intestinal inflammatory conditions
- •Bone marrow dysplasia
- •Have a known history of positive tests for HIV/AIDS, or have active hepatitis B or C (based on serology).
- •Are expected to need any other anti-cancer therapy or immunotherapy to be initiated during the study period.
- •Have clinically active or unstable CNS metastases as assessed by the treating physician.
研究组 & 干预措施
Arm A: LTX-315 monotherapy singe lesion
Cohort 1-3: First induction treatment (6 weeks): In week 1 the first index lesion will be injected Twice daily on 3 consecutive days. During week 2-6 the injection will be once a week.
Second induction treatment (6 weeks) and Maintenance treatment (20 weeks)- At week 7 the second index lesion will be injected with same dosing schedule as the first index lesion.
Cohort 4 and above: Once daily on 3 consecutive days week 1. Week 2-6 one injection per week. From week 8, one dosing days every 2 weeks.
干预措施: LTX-315 consecutive lesions (Drug)
Arm B: LTX-315 monotherapy in multiple concurrent lesions
Patients with at least one injectable lesion and one bystander lesion will receive LTX-315 to one or more lesions:
Once daily on 2 consecutive days week 1-3.
干预措施: LTX-315 (Drug)
Arm C
Patients with melanoma and at least one injectable lesion will receive LTX-315 to one or more lesions on two consecutive days week 1-3 in combination with ipilimumab given for 4 cycles every 3 weeks.
干预措施: LTX-315 + ipilimumab (Drug)
Arm D
Patients with TNBC and at least one injectable lesion will receive LTX-315 to one or more lesions on two consecutive days week 1-3 in combination with pembrolizumab given every 3 weeks.
干预措施: LTX-315 + pembrolizumab (Drug)
结局指标
主要结局
Dose limiting toxicity
时间窗: 21 days
Dose limiting toxicities (DLT) and the overall safety profile (adverse events (AE), laboratory assessments, physical findings and symptomatic assessment) of LTX-315 as monotherapy and in combination with ipilimumab or pembrolizumab.
次要结局
- Anti tumour activity in injected tumour(Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed)
- Complete response (irCR) and partial response (irPR)(Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed)
- Overall response rate (OR)(Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed)
- Disease control rate (CR + PR + SD)(Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed)
- Progression free survival (PFS)(Every 8 weeks from treatment start up to 24 months or first documented progression documented assessed)