A first-in-human, open-label, dose escalation followed by dose expansion phase I/IIa trial to evaluate the safety, preliminary efficacy and pharmacokinetics of intratumoral CyPep-1 monotherapy and in combination with pembrolizumab in patients with advanced solid cancers.
- Conditions
- Solid malignant tumors10027656
- Registration Number
- NL-OMON54523
- Lead Sponsor
- Cytovation ASA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 65
For Phase I and Phase IIa Arms A and C: 1. Histologically or cytologically confirmed locally advanced (unresectable) or metastatic tumors (solid tumor or lymphoma) with an accessible tumor lesion for intratumoral injection of CyPep-1 malignancy (including lymphomas) that is either: a. Refractory to standard-of-care treatment b. Have a disease for which there is no standard therapy considered appropriate. Metastatic deposits (including cutaneous/subcutaneous lesions and metastatic deposits in lymph nodes) of tumors for which IT injections may be performed are eligible. Pure cutaneous infiltrations (e.g., breast cancer cutaneous carcinomatosis) are ineligible. 2. 1 to 3 non-ulcerated transcutaneously accessible lesion(s) for injection and measurable as defined by iRECIST. All other tumor lesion(s) may be selected for efficacy follow-up, but will not be subjected to treatment with CyPep-1. 3. Presence of tumor lesion(s) (that have not been previously irradiated) suitable for biopsy at screening and at Week 6. For Arm C: 4. Confirmation of the presence of at least 1 liver metastasis by imaging. 5. Subjects must have measurable disease which is equal to one or more metastatic liver lesions that can be accurately and serially measured that are greater than 1 cm dimension and for which the longest diameter is greater or equal to 1 cm as measured by CT (computed tomography)scan or magnetic resonance imaging (MRI). The metastatic liver lesion must not be in an area that received prior localized therapies. 6. Metastatic liver lesion for injection with >50% radiological visible necrosis must be avoided and the lesion must be located where any tumor swelling will not lead to gall bladder tract obstruction or lead to bleeding risk. For Arm D: 7. Histologically or cytologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV: M1a and/or M1b) melanoma considered incurable by Standard of Care. For metastatic melanoma, only cutaneous, subcutaneous, lymph node, or lung metastases are allowed. 8. Previously exposed to ICI(s) and be categorized following the SITC Immunotherapy Resistance Taskforce (Kluger 2020) meeting one of the following: a. Have primary resistance: PD-(L)-1 inhibitor exposure >=6 weeks and have the best response as one of the following: i. PD, ii. SD for <6 months. b. Have secondary resistance: PD-(L)-1 inhibitor exposure >=6 weeks and best response CR, PR, or SD >6 months. c. Have adjuvant therapy resistance: recurrence subcategorized into primary resistance/early relapse occurred <12 weeks after the last dose, and late relapse occurred >=12 weeks after the last dose. If BRAF mutated, patients must have progressed to treatment with BRAF inhibitors. d. Have neoadjuvant therapy resistance including subjects with or without major pathologic response and subsequent PD that fulfills criteria for primary or secondary resistance e. Discontinued from ICI(s) therapy due to immune-related adverse events grade 3 or 4 other than endocrine insufficiencies treatable with hormonal replacement therapy, and meet one of the following: i. Remain on SD at discontinuation of PD-(L)1 inhibitor in combination with ipilimumab or show regrowth after <12 weeks of the last dose ii. Have not achieved a CR with single-agent PD-(L)1 inhibitor or combination of PD-(L)1 with LAG-3 inhibitor 9. At least 1 non-ulcerated lesion, not exceeding 5 cm in (the longest) diameter, for intratumoral injection(s) and measurable a
For Phase I and Phase IIa Arms A, C and D: subjects who meet ANY of the following criteria at screening will be excluded from trial entry: 1. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds delivered by IT injection to the to-be injected lesion(s), including investigational agents. Subjects with prior IT therapies are allowed in Arm D. 2. Participation in another clinical trial within 4 weeks prior to first dose of CyPep-1. 3. Anti-cancer therapy within 4 weeks prior to the first dose of CyPep-1 (within 2 weeks for palliative radiotherapy, within 1 week for endocrine therapy). 4. Major surgical procedure within 14 days prior to the first dose of CyPep-1. 5. Live vaccine within 30 days prior to first dose of CyPep-1. 6. Expected to require any other form of systemic or localized antineoplastic therapy while in this trial. Localized palliative radiotherapy for pain relief is allowed on tumor lesions that are not selected for evaluation of treatment response. 7. Clinical evidence of an active second malignancy that is progressing or requires active treatment, except for curatively treated early stage (carcinoma in situ or stage 1) carcinomas or non-melanoma skin cancer. 8. Active autoimmune disease requiring immunosuppressive therapy. 9. Any condition requiring continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive agents within 2 weeks prior to first dose of CyPep-1. Inhaled, intranasal or topical (only on areas outside the injected lesion(s)) and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active auto-immune disease. 10. Abnormal or clinically significant coagulation parameters: a. Prothrombin Time - International Normalized Ratio (PT-INR) ) >= 1.5 ULN b. Activated Partial Thromboplastin Time (APTT) ) >= 1.5 ULN Subjects being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the SmPC for the administered treatment. 11. Subjects on anticoagulants with temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy at the discretion of the investigator and/or per local standard of care) during treatment period. 12. Known hypersensitivity to any component of CyPep-1. 13. Prior allogeneic tissue/solid organ transplant, stem cell or bone marrow transplant. 14. Known active human immunodeficiency virus (HIV). Subject is eligible when normal levels of CD4 are present. 15. Central nervous system (CNS) metastasis that is symptomatic or progressing or that requires current therapy (e.g., evidence of new or enlarging CNS metastasis, carcinomatous meningitis or new neurological symptoms attributable to CNS metastasis). 16. QTcF > 480 ms, history of long or short QT syndrome, Brugada syndrome, or known history of QTc prolongation, or Torsade de Pointes. 17. Women who are pregnant or breastfeeding. 18. Any serious and/or unstable pre-existing medical, psychiatric or other condition which in the investigator*s opinion could interfere with subject safety, obtaining written informed consent, or compliance with the trial protocol. 19. Has an active acute or chronic infection requiring systemic therapy at the time of CyPep-1 injection. Note: Subjects treated for mild/moderate infection with oral antibiotics only may be included based on con
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoints:<br /><br>- Type and number of adverse events (AEs) according to National Cancer<br /><br>Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE)<br /><br>criteria v5.0, and additional safety parameters of CyPep-1 as monotherapy and<br /><br>in combination with pembrolizumab.<br /><br>- Dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) for<br /><br>determination of RP2D of CyPep-1 as monotherapy and treatment-limiting<br /><br>toxicities (TLTs) of CyPep-1 in combination with pembrolizumab.</p><br>
- Secondary Outcome Measures
Name Time Method