CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations

NCT04260529 | Completed Phase 1 Results DMC

• 4 other identifiers: CyPep-12019-003317-33KEYNOTE-D02MK-3475-D02
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 8

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 programmed cell death protein 1(anti-PD-1) antibody pembrolizumab. Additionally, the trial will monitor anti-tumor effects on both injected lesions and distant non-injected deposits.

Conditions

Advanced Solid Tumor Malignancy

Keywords

Cancer; Tumour; Oncology; Immunotherapy; Oncolytic; Cluster of Differentiation 8 (CD8)); Intratumoral; Neoplasm

Outcome Measures

Primary Outcomes (1)

• Type and Number of Adverse Events (AEs)

  According to National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) criteria v5.0, and additional safety parameters.

  From Informed Consent Form (ICF) signing until Follow Up (FU) or until End of Treatment (EoT) visit. After FU visit, only ongoing AEs or Serious Adverse Events (SAEs) related to CyPep-1 were collected. Duration: up to a maximum of 28 months.

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  up to approximately 28 months

Other Outcomes (2)

• Progression-free Survival (PFS)

  time from treatment start until disease relapse or disease progression (based on all lesions, using iRECIST) or death due to any cause, whichever occurred earliest (up to a maximum of 28 months)

• Overall Survival (OS)

  from start of study treatment to the date of death with a maximum of 28 months

Study Arms (8)

Phase I Cohort 1

EXPERIMENTAL

Dose escalation at 0.5 mg (milligrams)/mL, n=3

Drug: CyPep-1

Phase I Cohort 2

EXPERIMENTAL

Dose escalation at 2 mg/mL, n=5

Drug: CyPep-1

Phase I Cohort 3

EXPERIMENTAL

Dose escalation at 5 mg/mL, n=6

Drug: CyPep-1

Phase IIa: Arm A

EXPERIMENTAL

CyPep-1 5.0mg/mL Monotherapy

Drug: CyPep-1

Phase IIa Arm B

EXPERIMENTAL

The safety and tolerability of CyPep-1 in combination with pembrolizumab was evaluated in a cohort of 15 patients in total, using a staggered approach. Initially, 3 patients received CyPep-1 at Recommended Phase 2 Dose (RP2D) in combination with pembrolizumab once every 6 weeks (Q6W)

Drug: CyPep-1; Drug: Pembrolizumab 25 MG/ML [KEYTRUDA®]

Phase IIa Arm C Cohort 4

EXPERIMENTAL

The safety and tolerability of at least 2 dose levels of CyPep-1, the RP2D and the dose immediately below that, were evaluated when CyPep-1 was administered IT using ultrasound guidance to one metastatic lesion in the liver (Cohort 4: 2 mg/mL, n=6)

Drug: CyPep-1

Phase IIa Arm C Cohort 5

EXPERIMENTAL

The safety and tolerability of at least 2 dose levels of CyPep-1, the RP2D and the dose immediately below that, were evaluated when CyPep-1 was administered intratumoral (IT) using ultrasound guidance to one metastatic lesion in the liver. The RP2D (Cohort 5: 5 mg/mL, n=6).

Drug: CyPep-1

Phase IIa Arm D

EXPERIMENTAL

The safety and tolerability of CyPep-1 at RP2D was planned to be further evaluated with focus on assessing efficacy signals of CyPep-1 monotherapy in 30 patients with cutaneous melanoma.

Drug: CyPep-1

Interventions

CyPep-1 DRUG

Intratumoral injection

Phase I Cohort 1; Phase I Cohort 2; Phase I Cohort 3; Phase IIa Arm B; Phase IIa Arm C Cohort 4; Phase IIa Arm C Cohort 5; Phase IIa Arm D; Phase IIa: Arm A

Pembrolizumab 25 MG/ML [KEYTRUDA®] DRUG

IV infusion

Also known as: KEYTRUDA®

Phase IIa Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Phase I and Phase IIa Arms A and C:
• 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:
• Refractory to standard-of-care treatment
• 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.
• to 3 non-ulcerated transcutaneously accessible lesion(s) for injection and measurable as defined by Immune Response Evaluation Criteria in Solid Tumors (iRECIST). All other tumor lesion(s) may be selected for efficacy follow-up but will not be subjected to treatment with CyPep-1.
• Presence of tumor lesion(s) (that have not been previously irradiated) suitable for biopsy at screening and at Week 6.
• For Arm C:
• Confirmation of the presence of at least 1 liver metastasis by imaging.
• 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 computed tomography (CT) scan or magnetic resonance imaging (MRI). The metastatic liver lesion must not be in an area that received prior localized therapies.
• 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:
• Histologically or cytologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV: M1a) melanoma considered incurable by Standard of Care. For metastatic melanoma, only distal cutaneous, subcutaneous, or lymph node metastases are allowed.
• Previously exposed to ICI(s) and be categorized following the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce 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. Progressive disease/ Disease progression (PD), ii. Stable Disease (SD) for \<6 months. b. Have secondary resistance: PD-(L)-1 inhibitor exposure ≥6 weeks and best response Complete response (CR), Partial Response (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 B-Raf gene (BRAF) mutated, patients must have progressed to treatment with BRAF inhibitors.

You may not qualify if:

• 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:
• 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.
• Participation in another clinical trial within 4 weeks prior to first dose of CyPep-1.
• 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).
• Major surgical procedure within 14 days prior to the first dose of CyPep-1.
• Live vaccine within 30 days prior to first dose of CyPep-1.
• 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.
• 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.
• Active autoimmune disease requiring immunosuppressive therapy.
• 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.
• Abnormal or clinically significant coagulation parameters:
• Prothrombin Time - International Normalized Ratio (PT-INR) ≥ 1.5 ULN
• 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 Summary of Product Characteristics (SmPC) for the administered treatment.
• 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.
• Known hypersensitivity to any component of CyPep-1.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Cytovation AS: lead

Study Sites (8)

Institue Curie

Paris, France

Location

Institute Gustave Roussy

Villejuif, France

Location

NKI/AvL

Amsterdam, Netherlands

Location

LUMC

Leiden, Netherlands

Location

EMC

Rotterdam, Netherlands

Location

UMCU

Utrecht, Netherlands

Location

Vall d'Hebron (VHIO)

Barcelona, Spain

Location

START

Madrid, Spain

Location

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MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Limitations and Caveats

Recruitment of Arm D was stopped after the inclusion of 1 subject, as recruitment of arm D was not feasible in the current environment.

Results Point of Contact

• Title: CEO
• Organization: Cytovation ASA

contact@cytovation.com

+4747718809

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: April 30, 2020
• Primary Completion: July 5, 2024
• Study Completion: July 5, 2024
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 6 months of study completion

Locations

NL (4); FR (2); ES (2)