Melanoma

* Patients with histologically or cytologically confirmed diagnosis of mUM not amenable
to surgical resection
.
* Has at least 1 measurable and injectable tumor of ≥ 1 cm in longest diameter (≥ 1.5 cm in
the shortest axis for a lymph node [LN]) that is amenable to safe serial injections of RP2
and to serial radiographic measurement and that has not been previously treated by
operation, irradiation, ablation, embolization, sclerosis, or any other lesion directed or
regional therapy.

* Must be willing to consent to provide an archival tumor biopsy sample that was collected
within 90 days prior to first dose of study intervention (ie, Dose 1) or provide a fresh
tumor biopsy during screening or predose on the day of Dose 1. Patients must also
consent to provide on-treatment biopsies as per protocol.
Note: The archival tumor biopsy must be collected after completion of the patient’s most
recent prior anticancer therapy.
* Life expectancy of > 6 months as estimated by the Investigator.
* LDH ≤ 2 × upper limit of normal (ULN) based on central laboratory testing.
* Has adequate hematologic function based on central laboratory testing, including:
• White blood cell (WBC) count ≥ 2.0 × 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Hemoglobin ≥ 8 g/dL (without packed red blood cell [RBC] transfusion within 2 weeks of dosing)

* Has adequate hepatic function based on central laboratory testing, including:
• Total bilirubin ≤ 1.5 × ULN (except patients with known Gilbert Syndrome who must
have a total bilirubin of < 3.0 × ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase increased (ALT) ≤ 3.0 × ULN
• Alkaline phosphatase (ALP) ≤ 2.5 × ULN

* Has adequate renal function based on central laboratory testing, defined as serum
creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/minute (measured using
Cockcroft-Gault formula).
I 10. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio [INR] ≤ 1.3)
and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT)
≤ 1.5 × ULN, based on central laboratory testing.
Note: Patients who are on therapeutic doses of anticoagulants may be eligible on a
case-by-case basis following discussion with the Medical Monitor, if their pretreatment
target INR is < 2.5 and if such treatments can be interrupted or dose decreased as
medically appropriate around the time of RP2 injections and protocol-specified biopsies.
Patients on prophylactic doses of anticoagulants must have such agents temporarily held
for an appropriate duration before and after each RP2 injection and/or protocol-specified
biopsies. For patients requiring deep/visceral injection(s) of RP2, the INR must be
≤ 1.5 at the time of each injection.

* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

Key Eligibility Criteria:

Inclusion:
1. < 40 years of age at the time of enrollment
2. Patient must be a post-menarchal female and report that their initial menstrual period occurred > 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)
3. Newly diagnosed with first cancer, exclusive of breast cancer.
4. Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.
5. For patients < 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m^2 cumulative cyclophosphamide equivalent dose (CED). For patients ≥ 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.

Exclusion:
1. Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
2. Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
3. Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
4. Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted prior to study enrollment.
5. Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).

For pre-screening, please contact: Please reach out to the Disease specific research teams.