A Study to Evaluate the Safety and Efficacy of CyPep-1 in Combination With Pembrolizumab for the Treatment of Advanced or Metastatic Cancers

NCT05383170 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: CYP0032021-006804-34KEYNOTE-D11MK-3475-D11
• Study Type: interventional
• Target: 6
• Locations: 5 countries
• Sites: 25

Brief Summary

This Phase 1b/2a study will assess the efficacy, safety, and pharmacodynamics of CyPep-1 when administered directly into measurable tumor lesions in combination with the anti-PD-1 antibody pembrolizumab. Additionally, the study will assess anti-tumor effects of CyPep-1 on injected lesions and non-injected target lesions identified at baseline, as well as local and systemic immunological effects of CyPep-1 in combination with pembrolizumab.

Conditions

Advanced Head and Neck Squamous Cell Carcinoma; Advanced Breast Cancer; Advanced Melanoma

Keywords

Cancer; Tumour; Oncology; Immunotherapy; Oncolytic; CD8; Intratumoral; Neoplasm; itRECIST

Outcome Measures

Primary Outcomes (2)

• Frequency, and Seriousness of TEAEs

  Number of CyPep-1 related TEAEs per grading.

  For each subject, from the time of signing the ICF until 30 days (90 days for SAEs) after the last dose of study treatment up to a maximum of 18 months.

• Incidence of DLTs

  Number of DLTs

  Initial 6 weeks of treatment.

Secondary Outcomes (2)

• PFS Per RECIST v1.1

  Up to approximately 18 months

• OS Per RECIST v1.1

  Up to approximately 18 months

Study Arms (3)

Arm A: advanced or metastatic HNSCC

EXPERIMENTAL

The safety and tolerability of CyPep-1 in combination with pembrolizumab will be evaluated in a cohort of 30 subjects in total with advanced or metastatic HNSCC. CyPep-1 will be administered every 2 weeks (Q2W) and pembrolizumab will be administered following a Q6W schedule as per standard of care (SoC).

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

Arm B: advanced or metastatic melanoma

EXPERIMENTAL

The safety and tolerability of CyPep-1 in combination with pembrolizumab will be evaluated in a cohort of 30 subjects in total with advanced or metastatic melanoma. CyPep-1 will be administered every 2 weeks (Q2W) and pembrolizumab will be administered following a Q6W schedule as per standard of care (SoC).

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

Arm C: advanced or metastatic TNBC

EXPERIMENTAL

The safety and tolerability of CyPep-1 in combination with pembrolizumab will be evaluated in a cohort of 30 subjects in total with advanced or metastatic TNBC. CyPep-1 will be administered every 2 weeks (Q2W) and pembrolizumab will be administered following a Q6W schedule as per standard of care (SoC).

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

Interventions

CyPep-1 DRUG

Intratumoral injection

Arm A: advanced or metastatic HNSCC; Arm B: advanced or metastatic melanoma; Arm C: advanced or metastatic TNBC

Pembrolizumab 25 MG/ML [KEYTRUDA®] DRUG

IV infusion

Also known as: KEYTRUDA®

Arm A: advanced or metastatic HNSCC; Arm B: advanced or metastatic melanoma; Arm C: advanced or metastatic TNBC

Eligibility Criteria

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

You may qualify if:

• Is 18 years of age or older on the day of signing informed consent;
• Provides written informed consent and is able to comply with study procedures and assessments;
• Has measurable disease as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1;
• Has at least 1 non-ulcerated, measurable, and accessible lesion for intra-tumoral (IT) injection with a maximum diameter of 5 cm;
• Is able to provide tissue from a core or excisional biopsy at screening or has an acceptable stored tumor sample available that was collected within 90 days prior to screening;
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Has a life expectancy \>=3 months, as determined by the Investigator;
• Female patients of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before screening), post-menopausal, defined as spontaneous amenorrhea for at least 2 years, or with follicle-stimulating hormone in the post-menopausal range at screening;
• Female patients of childbearing potential (defined as \<2 years after last menstruation or not surgically sterile) must have a negative serum pregnancy test at screening and agree to use a highly effective method for contraception from the time of signing the ICF until at least 120 days after the last administration of CyPep-1.
• If a male patient is able to father children, he must agree to use 2 acceptable methods of contraception throughout the study (eg, condom plus permicidal gel). Sperm donation is not recommended from the time of signing the ICF until at least 120 days after the last administration of CyPep-1
• Has adequate organ function. Specimens must be collected within 72 hours prior to the start of study treatment at Cycle 1 Visit 1.
• Have histologically confirmed diagnosis of HNSCC (including nasopharyngeal squamous cell carcinoma);
• Have advanced or metastatic HNSCC incurable by standard of care therapies; and
• Have failed or progressed on or after prior platinum-based therapy OR has failed or progressed on or after treatment with a checkpoint inhibitor administered either as monotherapy or in combination with other therapies (if immune checkpoint inhibitor \[ICI\] eligible based on programmed cell death ligand 1 \[PD-L1\] status).
• Have histologically confirmed diagnosis of malignant melanoma;

You may not qualify if:

• Has only non-palpable cutaneous infiltrations (eg, breast cancer cutaneous carcinomatosis);
• Had anti-cancer therapy within 4 weeks prior to the first dose of CyPep-1 (2 weeks for palliative radiotherapy);
• Has participated in a clinical trial and received an investigational therapy within 30 days prior to the first dose of CyPep-1;
• Has received or will receive a live or live attenuated vaccine within 30 days prior to the first dose of CyPep-1; Note: Seasonal flu vaccines that do not contain live vaccine are permitted. Coronavirus Disease 2019 (COVID-19) vaccines are only permitted with documentation of the date of the vaccine if the last dose of vaccine was administered \>14 days prior to the first dose of CyPep-1. The COVID-19 booster vaccine must be administered at least 14 days prior to the first dose of CyPep-1 and is not allowed during the first 3 months of the Treatment Period.
• Has tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to the Screening Visit; Note: Patients who have had a known SARS-CoV-2 infection \>14 days prior to the Screening Visit are permitted at Investigator discretion and must present with no symptoms.
• Has had a major surgical procedure within 14 days prior to the first dose of CyPep-1;
• Is expected to require a systemic or localized antineoplastic therapy during participation in this study, excluding localized palliative radiotherapy to tumors not selected for evaluation of treatment response; Note: Use of denosumab for patients with bone metastasis is allowed.
• Is pregnant or breastfeeding;
• Has clinical evidence of a secondary malignancy actively progressing or requiring active treatment other than curative therapies for early stage (carcinoma in situ or Stage 1) carcinomas or non-melanoma skin cancer;
• Has had any autoimmune disease requiring immunosuppressive therapy (ie, use of disease modifying agents, corticosteroids, or immunosuppressive drugs) within 2 years prior to the first dose of CyPep-1; Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a condition requiring continuous systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive agents within 2 weeks prior to the 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 autoimmune disease;
• Has abnormal or clinically significant coagulation parameters as determined by the Investigator (eg, prothrombin time, international normalized ratio, activated partial thromboplastin time) unless patients are on anticoagulants in which case it must be within appropriate clinical levels; Note: Patients who are on anticoagulants must be able to switch to a low molecular weight heparin or equivalent prior to Cycle 1 Day 1 and continue during the Treatment Period.
• Has a significant history or clinical manifestation of any allergic disorders and/or Quincke's edema (as determined by the Investigator) capable of significantly altering the absorption of drugs, of constituting a risk when taking CyPep-1 or pembrolizumab, or of interfering with the interpretation of the data;
• Has a known hypersensitivity to any component of CyPep-1 or pembrolizumab;
• Has a history of adverse reactions from treatment with ICIs, including pembrolizumab, which resulted in discontinuation of ICI or pembrolizumab or has ongoing pembrolizumab-related toxicity event(s) as per treatment-limiting toxicity definitions, except patients with ongoing endocrine disorders that are managed with replacement therapy (ie, hypothyroidism related to prior pembrolizumab treatment);

Sponsors & Collaborators

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

Study Sites (25)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City Of Hope

Duarte, California, 91010, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

CHRU de Besançon

Besançon, France

Location

Institut Bergonie

Bordeaux, France

Location

CHU Lille

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

AP-HM - Hôpital de la Timone

Marseille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hôpital Saint Louis - AP-HP

Paris, France

Location

Institute Gustave Roussy

Villejuif, France

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Azienda Ospedaliero Universitaria Senese

Siena, Italy

Location

NKI/AvL

Amsterdam, Netherlands

Location

Maastricht UMC

Maastricht, Netherlands

Location

EMC

Rotterdam, Netherlands

Location

Vall d'Hebron (VHIO)

Barcelona, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, Spain

Location

Clinica Universidad de Navarra Pamplona

Pamplona, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

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MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Limitations and Caveats

Phase 1b of the study (ie, the first 6 patients enrolled) was successfully completed per protocol. Following a re-assessment of target indications for CyPep-1, it was decided not to initiate the Phase 2a part of the study.

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

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 20, 2022
• Study Start: March 21, 2023
• Primary Completion: September 23, 2024
• Study Completion: September 23, 2024
• Last Updated: November 28, 2025
• Results First Posted: November 28, 2025

Record last verified: 2025-10

Locations

FR (8); NL (3); IT (2); US (6); ES (6)