OBJECTIVES: Extensive research has been conducted to optimally estimate the value of a drug. The Memorial Sloan Kettering Cancer Center (MSKCC)-proposed Drug Abacus and incremental cost effectiveness ratio (ICER) frameworks attempt to estimate the value of oncology drugs, with the latter particularly useful in population medicine. The utility of these frameworks in assessing value of an immune-oncology (IO) agent in an ultra-orphan tumor is not well-documented. METHODS: A survival partition model was developed to compare costs, life years and QALYs for an IO drug vs chemotherapy over the patient’s lifetime. A threshold of $156,000 per QALY and per life year gained was used for the ICER and MSKCC frameworks, respectively. User-modifiable premiums for each dimension for Drug Abacus were varied from 1-3, whilst allowing corresponding variation in the thresholds from $84,000 to $226,000 per life year or QALY gained. Conservative assumptions (e.g. no premium for Research and Development) were employed throughout the analyses. RESULTS: The monthly value of the drug using the ICER framework ranged from $4,033-$14,978 when only survival was considered. Incorporating quality of life decreased the value by $1,315-$3,537, whilst the inclusion of toxicity increased the value by $1,687. Using Drug Abacus the value of the drug related to survival and strength of evidence ranged from $4,129-$11,209. Incorporating each of novelty, rarity, population health burden, unmet need and prognosis dimensions were estimated to increase the value by up to a maximum of $7,669, $15,338, $1,534, $15,338 and $12,599, respectively. CONCLUSIONS: For an ultra-orphan tumor, the additional value dimensions related to disease and drug-specific factors influence the value assessment. Overall, holistic assessment is needed to capture true value of a new IO therapy in rare diseases.