CyPep-1 Injections in Cancer Inducing Lymphocyte Infiltrate Accumulations

Inclusion criteria

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.
• 1 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.

c. Have adjuvant therapy resistance: recurrence subcategorized into primary resistance/early relapse occurred 15 mm in the longest diameter by > 10 mm in the short axis.

• Estimated life expectancy of at least 3 months.
• Human immunodeficiency virus (HIV) infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease.

Exclusion criteria

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