113
Enrolled / 125 Target
Simulated
66.7%
ORR CNS (MAPKi-naïve)
Verified
13.9m
Median DoR (CNS)
Verified
<2%
Discontinuation Rate
Verified
>75%
Clinical Benefit Rate
Verified
54
Sites (9 Countries)
Verified
Verified ORR/DoR
SUB-PROTOCOL A: CNS Tumors
BRAF V600 Primary CNS | RANO
25+/50
Enrolled*
66.7%
ORR ✓
13.9m
mDoR ✓
Interim analysis passed efficacy threshold (n=25) ✓
Verified ORR/DoR
SUB-PROTOCOL B: Solid Tumors
Other BRAF V600 | RECIST v1.1
--/25
Enrolled*
41.7%
ORR ✓
17.8m
mDoR ✓
Time to response: 3.5 months median ✓
No Data Yet
SUB-PROTOCOL C: Rare Tumors
Rare BRAF V600 (≤40K US/yr) | RECIST
--/25
Enrolled
--
ORR
--
mDoR
Includes: Ovarian, Cholangiocarcinoma, GI, NEC
No Data Yet
SUB-PROTOCOL D: BRAF Fusions
Class 2 Alterations | RECIST v1.1
--/25
Enrolled
--
ORR
--
mDoR
No MEK inhibitor combination required

Dual Response Criteria Assessment

Simulated Data
RECIST v1.1 (Solid Tumors)
Applies to: Cohort A, D
Assessments: Q9W (48W) → Q12W
CR Definition: Complete disappearance
PR Definition: ≥30% decrease SLD
CR8 (12%)■■
PR23 (35%)■■■■■
SD24 (36%)■■■■■
PD11 (17%)■■■
RANO HGG/LGG (CNS Tumors)
Applies to: Cohort B, C
Baseline: Post-RT MRI
Pseudoprogression: 12-week window monitored
Steroid Requirement: CR needs ≤2mg dex
CR6 (10%)■■
PR31 (53%)■■■■■■■
SD15 (25%)■■■■
PD7 (12%)■■

BICR / Imaging Core Lab

Operational Simulated
18
Pending QC
12
Reader 1
8
Reader 2
3
Adjudication
QC Pass Rate 96.2%
Reader Agreement (κ) 0.84
BTIP Compliance (CNS) 91.5%
⚠ RANO Alert: 4 cases in pseudoprogression window - confirmation scans pending

Safety Summary (Phase 1/2a, n=113)

Favorable Profile Verified
TEAE (Most Common) All Grade Grade 3+
LFT Elevations (ALT/AST) Grade 1-2 Rare
Fatigue Grade 1 0%
Nausea Grade 1 0%
Diarrhea Grade 1 0%
Headache (CNS pts only) Variable <5%
0
DLTs at RP2D
<2%
Discontinuation
No
Paradoxical Activation
vs BRAF/MEK Inhibitors: Lower rash, fever; reduced intratumoral bleeding, cardiac, ocular, growth effects

Efficacy by Tumor Category

Phase 1/2a (MAPKi-naïve) Verified
Tumor Category N ORR 95% CI
Primary CNS V600 (MAPKi-naïve) 9 66.7% [29.9-92.5]
→ LGG/Glioneuronal -- mPFS: NR [1.6-27.8+ mo]
→ HGG (Grade 3-4) -- mPFS: 6.7m [2.8-34.1 mo]
→ mDoR (Solid Tumors) -- 17.8m [3.7-59.2 mo]
→ Time to Response -- 3.5m Median
Note: Excludes CRC adenocarcinoma, pancreatic ductal, NSCLC, cutaneous melanoma (V600E), thyroid (ATC/PTC) per protocol

Top Enrolling Sites

Simulated Data
Site Country Enrolled Status
MD Anderson US 14 Top
Dana-Farber US 11 Top
Gustave Roussy FR 9 Top
Peter Mac AU 8 Good
Princess Margaret CA 7 Good

Duration of Response

Simulated Chart
[Kaplan-Meier DoR Curve by Cohort]
CNS: 13.9 mo (3.7-32.3) | Solid: 17.8 mo (3.7-59.2)
78%
6-month DoR Rate
62%
12-month DoR Rate

CNS Tumor Monitoring (RANO Requirements)

Simulated Data
Pseudoprogression
4
In 12-week window
Confirmation scans scheduled
Steroid Use
38%
On corticosteroids
12% on >2mg dex equivalent
Intracranial Response
63%
iORR (37/59)
6 CR, 31 PR
BTIP Imaging
91.5%
Protocol compliant
3D T1W + FLAIR per spec