Overview

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

Status:
Not yet recruiting
Trial end date:
2025-02-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Cytovation AS
Collaborator:
Merck Sharp & Dohme LLC
Treatments:
Pembrolizumab
Criteria
Inclusion Criteria:

General Inclusion Criteria

1. Is 18 years of age or older on the day of signing informed consent;

2. Provides written informed consent and is able to comply with study procedures and
assessments;

3. Has measurable disease as determined by the Response Evaluation Criteria in Solid
Tumors (RECIST) version (v)1.1;

4. Has at least 1 non-ulcerated, measurable, and accessible lesion for intra-tumoral (IT)
injection with a maximum diameter of 5 cm;

5. 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;

6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

7. Has a life expectancy >=3 months, as determined by the Investigator;

8. 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;

9. 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.

10. 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

11. Has adequate organ function. Specimens must be collected within 72 hours prior to the
start of study treatment at Cycle 1 Visit 1.

Inclusion Criteria for Arm A

A patient who meets all of the general Inclusion Criteria and the following additional
criteria will be eligible for inclusion in Arm A:

1. Has histologically confirmed diagnosis of HNSCC;

2. Has advanced or metastatic HNSCC incurable by standard of care therapies; and

3. Has 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).

Inclusion Criteria for Arm B

A patient who meets all of the general Inclusion Criteria and the following additional
criteria will be eligible for inclusion in Arm B:

1. Has histologically confirmed diagnosis of malignant melanoma;

2. Has advanced or metastatic melanoma incurable by standard of care therapies; and

3. Has failed or progressed on or after treatment with a checkpoint inhibitor
administered either as monotherapy or in combination with other checkpoint inhibitors
or other therapies.

Inclusion Criteria for Arm C

A patient who meets all of the general Inclusion Criteria and the following additional
criteria will be eligible for inclusion in Arm C:

1. Has histologically confirmed diagnosis of TNBC;

2. Has advanced or metastatic TNBC incurable by standard of care therapies; and

3. Has failed or progressed on or after treatment with a checkpoint inhibitor
administered either as monotherapy or in combination with other therapies (if ICI
eligible based on PD-L1 status) OR has received prior systemic therapy with either an
anthracycline- or taxane-containing regimen (if ICI non-eligible based on PD-L1
status).

Exclusion Criteria:

1. Has only non-palpable cutaneous infiltrations (eg, breast cancer cutaneous
carcinomatosis);

2. Had anti-cancer therapy within 4 weeks prior to the first dose of CyPep-1 (2 weeks for
palliative radiotherapy);

3. Has participated in a clinical trial and received an investigational therapy within 30
days prior to the first dose of CyPep-1;

4. 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.

5. 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.

6. Has had a major surgical procedure within 14 days prior to the first dose of CyPep-1;

7. 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.

8. Is pregnant or breastfeeding;

9. 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;

10. 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.

11. Has a condition requiring continuous systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalents) 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;

12. 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.

13. 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;

14. Has a known hypersensitivity to any component of CyPep-1 or pembrolizumab;

15. 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);

16. Has an active infection requiring systemic therapy;

17. Has known history or active Hepatitis B virus or Hepatitis C virus infection;

18. Has had radiotherapy within 2 weeks prior to the first dose of CyPep-1, is in recovery
from radiation toxicity, or has had radiation pneumonitis;

19. Has a history of non-infectious pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease;

20. Has had a prior allogeneic tissue/solid organ transplant, stem cell, or bone marrow
transplant;

21. Has active human immunodeficiency virus (HIV). Patient is eligible when on stable
antiretroviral therapy (no change in medication or dose) for at least 4 weeks prior to
screening, has confirmed virologic suppression with HIV RNA less than 50 copies/mL or
the lower limit of quantification (below the limit of detection) using the locally
available assay at the time of screening and for at least 12 weeks prior to screening,
and has a cluster of differentiation 4+ T cell count >350 cells/mm3 at screening.
HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman
Disease will be excluded;

22. Has a central nervous system (CNS) metastasis that is symptomatic, progressing, or
that requires current therapy (eg, evidence of new or enlarging CNS metastasis,
carcinomatous meningitis, or new neurological symptoms attributable to CNS
metastasis);

23. Has a QTcF >480 ms at screening, history of long or short QT syndrome, Brugada
syndrome, QTc prolongation, or Torsade de Pointes, with the exception of patients with
controlled atrial fibrillation, pacemaker, or bundle branch block as the QTc will be
prolonged due to the widened QRS; or

24. Has a history of or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or make participation in the study
not in the best interest of the patient, in the opinion of the Investigator.