A study to assess the safety and tolerability of multiple doses of CyPep-1 in subjects with advanced cancer.
- Conditions
- Histologically or cytologically confirmed locally advanced (unresectable) or metastatic tumors (solid tumors or lymphoma) with an accessible tumor lesion for intratumoral injection of CyPep-1 that meet one of the following criteria:a. Relapsed following or progressed through standard therapyb. Have a disease for which no standard effective therapy exists.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003317-33-NL
- Lead Sponsor
- Cytovation ASA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 84
MAIN Criteria: Limited characters
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 that is either refractory to standard-of-care treatment or have a disease for which there is no standard therapy considered appropriate.
2.1-3 non-ulcerated transcutaneously accessible lesion(s) for injection and measurable as defined by iRECIST.
3. Presence of tumor lesion(s) (that have not been previously irradiated) suitable for biopsy at screening and at Week 6.
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 = 1 cm as measured by CT scan or MRI.
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 bleeding risk.
Arm D:
7. Histologically or cytologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV: M1a and/or M1b) melanoma considered incurable.
8. Previously exposed to ICI(s) and be categorized following the SITC Immunotherapy Resistance Taskforce meeting one of criteria listed in protocol
9. At least 1 non-ulcerated lesion, not exceeding 5 cm in (the longest) diameter, for intratumoral injection(s) and measurable as defined by iRECIST.
10. Resolution of toxicity due to prior therapy returned to baseline or < Grade 2, except for alopecia or other irreversible immune-mediated AEs, as defined by CTCAE v5.0. and SITC ICI-related AEs.
11.Prior treatment(s) delivered by IT injection to the to-be injected lesion(s), including investigational agents, is allowed.
Phase I and Phase IIa Arms A, C and D in addition:
12.Age = 18 years.
13.Estimated life expectancy of at least 3 months.
14.Eastern Cooperative Oncology Group Performance Status of 0 or 1
15.Resolution of toxicity due to prior therapy to Grade < 2 (except for alopecia and transaminases in case of liver metastases) as defined by CTCAE v5.0.
16.Ability to give written informed consent and to comply with the protocol.
17.WOCBP must have a negative highly sensitive pregnancy test at screening and agree to use highly effective method for contraception at least 120 days after the last administration of CyPep-1. The partners of WOCBP must also apply contraceptive methods and are recommended not to donate sperm.
18. A male participant must agree to use contraception and refrain from sperm donation during the treatment period and for at least 120 days after the last dose of trial medication.
19.Adequate bone marrow, liver, and renal function
For Phase IIa Arm B:
20.The participant provides written informed consent for the trial.
21.Age =18 years
22.Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumor malignancy that is refractory to SoC treatment or for which there is no appropriate standard therapy. Metastatic deposits of tumors for which IT injections may be performed are eligible. Pure cutaneous infiltrations are ineligible.
23.Subjects must have progressed on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administ
MAIN Criteria: Limited char.
Phase I and Phase IIa Arm A, C and D:
1.prior treatment(s) with 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
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.
7.Clinical evidence of an active second malignancy that is progressing or requires active treatment, except for curatively treated early stage carcinomas or non-melanoma skin cancer.
8.Active autoimmune disease requiring immunosuppressive therapy.
9.Any condition requiring continuous systemic treatment with either corticosteroids
or other immunosuppressive agents within 2 weeks prior to first dose of CyPep-1.
10.Abnormal or clinically significant coagulation parameters: PT-INR + APTT
11.Subjects on anticoagulants with temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy) 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 metastasis that is symptomatic or progressing or that requires current therapy
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.
Additional for Phase IIa Arm C:
20.Subject is a candidate for hepatic surgery or local regional therapy of liver metastases with curative intent.
21.More than 1/3 of the liver is estimated to be involved with metastases.
22.There is invasion by cancer into the main blood vessels.
23.Subject is currently receiving or has received liver metastatic-directed therapy less than 4 weeks prior to enrolmentor hepatic surgery.
Phase IIa Arm B:
Some criteria for arm B correspond to criteria for Phase I and Arm A and C. Due to the character limitation only a reference to these sections is listed below.
24.17
25.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher irAE.
26.Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (within 1 week for endocrine therapy) prior to first dose of CyPep-1.
27.Has received prior (palliative) radiotherapy within 2 weeks of start of trial treatment.
28.2
29.1
30.6
31.Ongoing pembrolizumab-related toxicity event(s) as per TLT definition.
32.2
33.Has had an allogeneic tissue/solid organ transplant.
34.Has a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method