Treatment Window
S3 WithdrawThe immune system is withdrawing from the fight. This is the critical decision point. Checkpoint blockade can re-engage the immune response, but the window is closing. Delay significantly reduces response probability.
▲ HIGH URGENCY — treatment window closing
Fight Ratioi
Likely Responder2.3×
Immune advantage
(adjusted: 2.2×)
Immune system has a clear advantage over tumour proliferation. Checkpoint blockade is structurally indicated.
Step Coverage Analysis
2/4 StepsDetection
Open
Priming
Carboplatin
Encounter
Pembrolizumab
Maintenance
Open
| Agent | Step | Mechanism |
|---|---|---|
| Pembrolizumab | — | — |
| Carboplatin | — | — |
| Pemetrexed | — | — |
Open Escape Routes
Detection, Maintenance
steps uncovered.
The tumour can escape through
these routes.
Adding a TIGIT inhibitor would NOT help — it covers the same Encounter step as the current PD-1/PD-L1 agent.
Structural Recommendations
Do not add Pemetrexed
Pemetrexed covers the same step (Priming) as Carboplatin. No additional escape route closed.
Consider LAG-3 inhibitor if available
LAG-3 addresses antigen presentation (Detection step) — genuinely different from PD-1.
FULCRUM CDS is a structural analysis tool. It does not replace clinical judgement. All treatment decisions must be made by the treating physician. Predictions derive from the coverage principle — structural theory, not fitted models. Not FDA approved.
Trial Evidence — NSCLC — Adenocarcinoma
Observed ORR| Regimen | Trial | ORR | n | Year |
|---|---|---|---|---|
| carbo+pem+pembro_l | KEYNOTE-189 | 47.6% | 410 | 2018 |
| pembro_l | KEYNOTE-024 | 44.8% | 154 | 2016 |
| pembro_l | KEYNOTE-042 (all-comers) | 27.0% | 637 | 2019 |
| carbo+pem | KEYNOTE-189 ctrl | 18.9% | 206 | 2018 |
Source: published Phase II/III trial results. These are observed outcomes, not model predictions.