⁃ I 1. Male or female ≥ 18 years of age. I 2. (HCC only) Has locally advanced unresectable, recurrent, and/or metastatic HCC, with the diagnosis confirmed by histologic or cytologic analysis or clinical features or imaging criteria (using LI-RADS v2018; \[Chernyak 2018\]) according to the American Association for the Study of Liver Diseases criteria for patients with cirrhosis (Marrero 2018). Sites should select lesions that are either probable HCC - LIRADS 4 or definite HCC - LIRADS 5.

⁃ I 3. (HCC only) Must have progressed while on first and only systemic therapy, which must have included anti PD-1 or anti-PD-L1 therapy (eg, atezolizumab plus bevacizumab combination, durvalumab plus tremelimumab combination, durvalumab, pembrolizumab, or nivolumab monotherapy or nivolumab in combination with ipilimumab) as their immediate prior treatment regimen.

⁃ I 4. (HCC only) Child-Pugh A, determined within 14 days before first study treatment.

⁃ I 5. Has at least 1 measurable tumor of ≥ 1 cm in longest diameter (or ≥ 1.5 cm shortest diameter for lymph nodes) as defined by RECIST 1.1.

⁃ I 6. Has injectable tumor(s), which alone or in aggregate, total at least 1 cm in diameter.

⁃ I 7. Must be willing to consent to provide fresh tumor biopsy sample or archival tumor biopsy sample obtained within 90 days before the first dose of study treatment.

⁃ I 8. Has adequate hematologic function, including: White blood cell (WBC) count ≥ 2.0 × 109/L; absolute neutrophil count (ANC) ≥ 1.5 × 109/L (without granulocyte-colony stimulating factor support); platelet count ≥ 75 × 109/L (without transfusion); hemoglobin ≥ 8.5 g/dL (may have received transfusions; however, patient must not be transfusion-dependent).

⁃ I 9. Has adequate hepatic function including: total bilirubin ≤ 3.0 × upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 5.0 × ULN.

⁃ I 10. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/minute (measured using Cockcroft-Gault formula).

⁃ I 11. Serum albumin ≥ 2.8 g/dL. I 12. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.7) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

⁃ I 13. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

⁃ I 14. Female and male patients who meet the following criteria:

• Female patients are eligible if not pregnant (see IC #15) or breastfeeding and if one of the following applies 1) is a woman of non-childbearing potential (WNCBP) OR 2) is a woman of childbearing potential and must agree to use a highly effective contraception method during the treatment period, and for at least (a) 90 days after the last dose of RP2 or (b) 5 months after the last dose of atezolizumab, or (c) 6 months after the last dose of bevacizumab, or (d) 90 days after the last dose of durvalumab, whichever is longer.

• Male patients are eligible to participate if they agree to the following during the study treatment period, and for at least 90 days after the last dose of RP2: refrain from donating fresh unwashed sperm plus either be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) OR must agree to use an external condom and also should advise their partner to use a highly effective method of contraception as a condom may break or leak.

⁃ I 15. Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of β hCG within 72 hours before the first dose and a negative urine pregnancy test on Dose 1 Day 1.

⁃ I 16. Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form and in this protocol.

⁃ I 17. (BTC only) Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma whose disease has not progressed following the concurrent treatment with gemcitabine, platinum containing chemotherapy, and checkpoint inhibitors.

⁃ Patients must be on combination treatment with gemcitabine, platinum containing chemotherapy, and a checkpoint inhibitor for a minimum of 12 weeksand maximum of 24 weeks. After the last combination chemotherapy treatment (gemcitabine plus platinum chemotherapy), checkpoint inhibitor treatment must be limited to 2 doses (8 weeks).

⁃ Note: Patients who develop toxicity and discontinue platinum containing chemotherapy per treating physicians may enroll into the trial as long as they receive gemcitabine and durvalumab for 12 weeks. SD or PR must be documented on at least 2 scans while on prior combination treatment; the second scan can be the same as the baseline scan.