FULCRUM — Aisha Patel

Treatment Window

S3 Withdraw

The 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.

Critical question: Does the immune system have enough firepower?
If Immune Advantage is above 1.0×, checkpoint blockade can re-engage the retreating immune system. If below 1.0×, ICI alone is unlikely to be sufficient.

▲ HIGH URGENCY — treatment window closing

Immune Advantagei

Likely Responder

4.9×

Immune advantage (adjusted: 4.8×)

Immune system has a clear advantage over tumour proliferation. Checkpoint blockade is structurally indicated.

Structural analysis available

If scRNA-seq data with cell type annotations is available, enter the fractions below for structural drain/signal analysis.

CCR8+ TregPrimary drain

FGFBP2+ NKInnate signal

FOXP3+ TregSecondary drain

Step Coverage

2/4 Steps

✓

Detection

Fianlimab

⚠

Priming

Open

✓

Encounter

Cemiplimab

⚠

Maintenance

Open

Agent	Step	Mechanism
Fianlimab	—	Anti-LAG-3 — restores T cell differentiation
Cemiplimab	—	Anti-PD-1 — releases T cell brake

Open Escape Routes

Priming, Maintenance steps uncovered. Adding a TIGIT inhibitor would NOT help — same Encounter step.

Structural Recommendations

Consider adding CTLA-4 (ipilimumab/tremelimumab)

CTLA-4 operates at the Priming step — a different mechanism from PD-1. Extends coverage.

FULCRUM CDS is a structural analysis tool. It does not replace clinical judgement. Not FDA approved.

Trial Evidence — Melanoma — cutaneous

Observed ORR

Regimen	Trial	ORR	n	Year
dab+tram	COMBI-d	69.0%	211	2015
bini+enco	COLUMBUS	63.0%	192	2018
ipi+nivo	CheckMate 067	58.0%	314	2015
nivo	CheckMate 066	40.0%	210	2015
pembro_m	KEYNOTE-006	33.7%	279	2015
ipi	MDX010-20	10.9%	137	2010

Source: published Phase II/III trial results. Observed outcomes, not model predictions.

Tumour Immune Profile

GZMB

6.2 log₂

PRF1

5.8 log₂

IFNG

5.1 log₂

GZMA

5.9 log₂

MKI67

5.5 log₂

Immune Adv.

4.9×

Host Drain

IL1B

2.4 log₂

CXCL8

1.9 log₂

SPP1

3.1 log₂

Host Capacity

Albumin

4.1 g/dL

NLR

3.1

TMB

18.7 mut/Mb

PD-L1 TPS

60 %

LDH

240 U/L

Timeline

Sep 2025

Diagnosis — Stage IV melanoma, brain met negative

Oct 2025

Molecular — BRAF V600E+, TMB 18.7, PD-L1 60%

Nov 2025

RNA-seq — immune profiling completed

Mar 2026

Treatment decision — fianlimab + cemiplimab proposed

—

Initiate LAG-3 + PD-1 combination

New Patient

SMART on FHIR · FULCRUM v0.2.0 · generativegeometry.science