CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations
- Conditions
- Advanced Solid Tumor Malignancy
- Interventions
- Registration Number
- NCT04260529
- Lead Sponsor
- Cytovation AS
- Brief Summary
This Phase I/IIa trial is designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of CyPep-1 when administered directly into malignant tumors in monotherapy and in combination with anti-PD-1 antibody pembrolizumab. Additionally, the trial will monitor anti-tumor effects on both injected lesions and distant non-injected deposits.
- Detailed Description
Treatment with immune modulating agents may result in long lasting anti-tumor responses in patients with cancer. However, only a subset of patients obtains durable remission. Treatment strategies that aim at recruiting tumor antagonizing cellular components of the immune system holds great promise. CyPep-1 is a chemically synthesized peptide with oncolytic properties. It selectively targets cancer cells based on their altered molecular composition, and removes the surrounding cell membrane. This releases tumor neoantigens to the microenvironment and potentially induces an anti-tumour immune response.
Preclinical studies showing that CyPep-1 can synergize with anti-PD-1 antibody treatment in terms of decreased tumor volumes and prolonged survival highlight the possible clinical utility of CyPep-1 in the combination setting with ICIs.
This is a phase I/IIa, open label trial, with a dose escalation phase to evaluate the safety and tolerability of CyPep-1 as monotherapy and in combination with pembrolizumab, to identify the recommended phase 2 dose, followed by a dose expansion phase in subjects with advanced solid tumors. The trial consists of two phases and multiple arms.
Secondary objectives are preliminary anti-tumor efficacy and to assess the pharmacokinetics (PK) of CyPep-1 as monotherapy and in combination with pembrolizumab. As part of the exploratory analysis, it is planned to determine local and systemic immunological effects after CyPep-1 administration, alone and in combination with pembrolizumab.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D: CyPep-1 monotherapy melanoma CyPep-1 The safety and tolerability of CyPep-1 at RP2D will be further evaluated with focus on assessing efficacy signals of CyPep-1 monotherapy in subjects with melanoma. CyPep-1 administration is planned as QW injections until the second iRECIST/itRECIST assessment at week 16, followed by a Q2W dosing scheme. Arm C: CyPep-1 monotherapy liver lesions CyPep-1 The safety and tolerability of at least two dose levels of CyPep-1, the RP2D and the dose immediately below that, are planned to be evaluated when CyPep-1 is administered intratumorally to a metastatic lesion in the liver. CyPep-1 administration is planned as Q2W injections. Arm A: CyPep-1 monotherapy CyPep-1 Phase I of the trial, dose escalation, safety and tolerability will be documented and the MTD/RP2D will be determined. Cohorts of 3 subjects (in total 12 subjects) will receive IT injections with CyPep-1 by intratumoral injection at Day 1 of weeks 1, 3 and 5. In Phase IIa of the trial, dose expansion, the safety and tolerability will be further evaluated in an expanded cohort of 9 subjects at the RP2D of CyPep-1, determined in Phase I. CyPep-1 administration is planned as Q2W injections Arm B: CyPep-1 in combination with pembrolizumab CyPep-1 The safety and tolerability of CyPep-1 in combination with pembrolizumab will be evaluated in a cohort of 15 subjects in total, using a staggered approach. CyPep-1 will be administered every 2 weeks (Q2W) and pembrolizumab will be administered following a Q6W schedule as per standard of care (SoC). Arm B: CyPep-1 in combination with pembrolizumab Pembrolizumab 25 MG/ML [KEYTRUDA®] The safety and tolerability of CyPep-1 in combination with pembrolizumab will be evaluated in a cohort of 15 subjects in total, using a staggered approach. CyPep-1 will be administered every 2 weeks (Q2W) and pembrolizumab will be administered following a Q6W schedule as per standard of care (SoC).
- Primary Outcome Measures
Name Time Method Dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) for determination of RP2D of CyPep-1 6 weeks DLTs according to CTCAE v5.0
Type and number of adverse events (AEs) 2 weeks According to National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) criteria v5.0, and additional safety parameters.
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) at RP2D in injected lesions 8 weeks Defined by complete and partial responses, according to Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Trial Locations
- Locations (8)
Vall d'Hebron (VHIO)
🇪🇸Barcelona, Spain
NKI/AvL
🇳🇱Amsterdam, Netherlands
Institute Gustave Roussy
🇫🇷Villejuif, France
Institue Curie
🇫🇷Paris, France
LUMC
🇳🇱Leiden, Netherlands
EMC
🇳🇱Rotterdam, Netherlands
UMCU
🇳🇱Utrecht, Netherlands
START
🇪🇸Madrid, Spain