IO-resistant metastatic melanoma — progression on prior anti-PD-1 (± anti-CTLA-4 or anti-...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-MELANOMA-IO-RESISTANT`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-MELANOMA`
Sources	`SRC-C14401-CHESNEY-2024` `SRC-CHECKMATE-067-LARKIN-2019` `SRC-ESMO-MELANOMA-2024` `SRC-NCCN-MELANOMA-2025`

Red Flag Origin

Definition	IO-resistant metastatic melanoma — progression on prior anti-PD-1 (± anti-CTLA-4 or anti-LAG-3) regimen. Treatment shifts to BRAFi+MEKi salvage (if BRAF V600 mutant) OR lifileucel TIL (C-144-01 — ORR 31% post-IO post-BRAFi); ipi-nivo rechallenge in selected cases.
Clinical direction	intensify
Category	transformation-progression
Shifts algorithm	ALGO-MELANOMA-METASTATIC-2L

Trigger Logic

{
  "all_of": [
    {
      "finding": "prior_io_received",
      "value": true
    },
    {
      "any_of": [
        {
          "finding": "progression_on_io",
          "value": true
        },
        {
          "finding": "io_response_status",
          "value": "progression"
        },
        {
          "finding": "io_response_status",
          "value": "primary_resistance"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

Lifileucel (C-144-01 / TILVANCE-301) — first FDA-approved TIL therapy in solid tumors (Feb 2024). Eligibility: ECOG 0-1, prior anti-PD-1 + anti-CTLA-4 (if eligible) + BRAFi+MEKi (if BRAF mut). Resectable metastasis required for TIL harvest. Lymphodepletion (cy + flu) + IL-2 administration → ICU-grade supportive care. BRAFi+MEKi salvage post-IO has lower response rates (ORR 30-40%) than 1L (ORR 65-75%) — sequencing matters. Ipi-nivo rechallenge data (CheckMate-064 / 069) — modest response in select patients.

Used By

Algorithms

ALGO-MELANOMA-METASTATIC-2L - ALGO-MELANOMA-METASTATIC-2L