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. - CICILIA

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Subjects with incurable advanced or metastatic solid tumor malignancy for whom no treatment options exist and who have tumor lesion that is accessible for intratumoral injection of CyPep-1.

• Registration Number: EUCTR2019-003317-33-ES
• Lead Sponsor: Cytovation AS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-23
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

MAIN Criteria: Limited characters
Phase I and Phase IIa Arm A:
1.Histologically 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.
2.1-3 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 treated with CyPep-1.

Arm C:
3.Confirmation of the presence of at least 1 liver metastasis by imaging.
4.Disease progression during or after one or more prior SoC systemic anti cancer therapy for metastatic disease or progression during or within 6 months of receiving adjuvant therapy. If subjects, are deemed not appropriate for systemic anti-cancer therapy for metastatic disease or if they refuse it, they may be eligible after investigator discussion with Sponsor and medical monitor for approval.
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. 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 bleeding risk.

Phase I and Arms A and C in addition:
7.Presence of tumor lesion(s) (that have not been previously irradiated) suitable for biopsy at screening and at Week 6.
8.Age = 18 years.
9.Estimated life expectancy of at least 3 months.
10.Eastern Cooperative Oncology Group Performance Status of 0 or 1
11.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.
12.Ability to give written informed consent and to comply with the protocol.
13.All subjects of childbearing potential must have a negative highly sensitive pregnancy test at screening and agree to use highly effective method for contraception according to the EU CTFG guidance from time of signing the ICF until at least 120 days after the last administration of CyPep-1. The partners of subjects with childbearing potential must also apply contraceptive methods and are recommended not to donate sperm.
14.Adequate bone marrow, liver, and renal function

For Arm B:
15.The participant (or LAR) provides written informed consent for the trial.
16.Age ? 18 years
17.Participant with histologically 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.
18.Subjects must have progressed if on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the listed in the protocol.
19.A male participant must agree to use contraception and refrain from sperm donation during the treatment period and for

Exclusion Criteria

MAIN Criteria: Limited characters
Phase I and Arm A and C:
1.prior treatment(s) with compounds delivered by IT injection to the to-be injected lesion(s), including investigational agents.
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 for whom temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy) during treatment period, is not an option
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.

Additional for Arm C:
19.Subject is a candidate for hepatic surgery or local regional therapy of liver metastases with curative intent.
20.More than 1/3 of the liver is estimated to be involved with metastases.
21.There is invasion by cancer into the main blood vessels.
22.Subject is currently receiving or has received liver metastatic-directed therapy less than 4 weeks prior to enrolmentor hepatic surgery.

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.
23.17
24.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.
25.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.
26.Has received prior (palliative) radiotherapy within 2 weeks of start of trial treatment.
27.5
28.1
29.6
30.Ongoing pembrolizumab-related toxicity event(s) as per TLT definition.
31.2
32.Has had an allogeneic tissue/solid organ transplant.
33.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of CyPep

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified