Dose-finding strategy page: BX-401

A specimen of the artifact, filled in for an invented program

trial design

dose finding

immunology

working document

The one-page TCE dose-finding strategy filled in for an invented CD20xCD3 program at the end of dose escalation, followed by the blank template.

Published

September 11, 2026

BX-401 does not exist. The program, the doses, the dates and the findings below are invented to show what a filled page looks like. No number here is a measurement, and nothing here should be read as a statement about any real T-cell engager. Owners are given as roles rather than names for the same reason. The specification for the page is here.

Program BX-401, CD20xCD3 T-cell engager · Indication relapsed follicular lymphoma · Stage end of escalation, entering expansion

Page owner Clinical pharmacology lead · Revised 2026-09-11 · Next revision before the Gate 2 meeting, November 2026

Objective. Phase 1/1b characterizes safety, PK, PD and preliminary activity across the 15 to 120 mg full-dose range. The objective is to carry a sufficiently characterized set of doses into Phase 2b optimization, not to select one dose.

Decisions

Live decisions. ○ Open, ◐ Working, ● Locked. ✅ Agreed, ⚠️ Split, – Not asked. ⏰ evidence lands after the decision is due.
Decision	Current position	State	Team	Decide by	Evidence	Owner
Step-up levels	0.5 / 3 / 15 mg	● Locked (amendment, ~3 mo)	⚠️ Split: Translational wants 2 steps	Ph2 protocol, Q1 27	⏰ CRS by step, cohorts 1–6; reads out Feb 27	ClinPharm lead
Premedication	Dexamethasone before each step-up	◐ Working	⚠️ Split: Safety wants it before full doses too	Ph2 protocol, Q1 27	⏰ Pooled CRS by premed use; not randomized, so confounded	Safety lead
Monitoring	Overnight after each step-up	◐ Working	– Not asked	Ph2 protocol, Q1 27	CRS onset times from expansion	Early Dev lead
Re-priming after a gap	Restart full step-up after >6 weeks missed	○ Open	– Not asked	Ph2 protocol, Q1 27	⏰ Class precedent only; no program data planned	ClinPharm lead
Stop escalation	Stop at 120 mg or at a depletion plateau	◐ Working	⚠️ Split: disease team wants 240 mg explored	At the 120 mg cohort	Exposure-response on B-cell depletion and response rate	Early Dev lead
Doses to expand	30 and 120 mg	◐ Working	✅ Agreed	Gate 2, Nov 26	Escalation PK and depletion; expansion slots are the constraint	Early Dev lead
Number carried forward	2	◐ Working	✅ Agreed	Gate 3, Q2 27	Project Optimus expects a randomized comparison	Program team
Which doses carried forward	TBD among 30, 60, 120 mg	○ Open	– Not asked	Gate 3, Q2 27	⏰ Expansion exposure-response at the Q3 27 interim	ClinPharm lead
Full-dose interval	Q2W after cycle 3	○ Open	– Not asked	Ph2 protocol, Q1 27	⏰ PK simulation only; no program data on Q2W	ClinPharm lead
Maintenance	None assumed	○ Open	⚠️ Split: Late Dev assumes maintenance in the Ph3 plan	Gate 4, 2028	⏰ Nothing planned that would answer it	Late Dev lead

Settled. Starting dose 0.5 mg, MABEL-derived, locked at protocol v1, 2025-03. · Route and scaling: subcutaneous, fixed dose, locked at Gate 0, 2025-03. · Number of step-up doses: 3, locked at protocol v1, 2025-03. · Interval between step-ups and to the first full dose: 7 days, locked at protocol v1, 2025-03.

Carry forward

How many: 2. Which: TBD among Low (30 mg), Mid (60 mg), High (120 mg).

Carry-forward candidates
Candidate	Dose and exposure	Role
Low	30 mg, ~0.4× the exposure at 120 mg	Lower end of the effective range; the only candidate that does not require an overnight stay at full dose
Mid	60 mg, ~0.7×	Intermediate benefit-risk; not yet given to any patient
High	120 mg, reference	Incremental benefit and the upper range; the dose the expansion will characterize

Why this number and spread. Two doses with roughly a three-fold exposure separation are enough to characterize exposure-response in Phase 2b. Project Optimus expects more than one dose in a randomized comparison, so one dose is not an option the program has. Which two stays TBD until the expansion exposure-response interim, and the pair will be Low with High unless the interim shows Low short of adequate activity.

Escalate, expand, stop

Escalate when acute safety at the current level is acceptable over 21 days, CRS is manageable with the current premedication, exposure is below the target range, and B-cell depletion is incomplete.

Expand when the dose sits in a plausible therapeutic range and what limits the next decision is patient numbers rather than dose levels.

Stop escalating when depletion is complete and sustained, exposure-response on the response rate has plateaued, or toxicity exceeds the protocol definition. Reaching a maximum tolerated dose is not required.

Gates

flowchart LR
    P["Gate 0<br/>Protocol<br/>2025-03 ✓"] --> E["Gate 1<br/>Escalate<br/>per cohort"]
    E --> X["Gate 2<br/>Expand / stop<br/>Nov 2026"]
    X --> C["Gate 3<br/>Carry forward<br/>Q2 2027"]
    C --> O["Gate 4<br/>Optimize<br/>2028"]
    O --> R["Registrational<br/>dose and regimen"]

Three rows are on the critical path. Which doses carry forward needs the Q3 2027 interim and is due at Gate 3 in Q2 2027. Full-dose interval and re-priming after a gap are both due at the Phase 2 protocol with nothing planned that would answer either, so both will be decided on prior information and the page should say so once that is agreed.

The blank template

Copy this, delete the specimen content, keep the markers.

**Program** · **Indication** · **Stage**

**Page owner** · **Revised** · **Next revision**

**Objective.** One or two sentences.

| Decision | Current position | State | Team | Decide by | Evidence | Owner |
|:---|:---|:---|:---|:---|:---|:---|
|  |  | ○ Open / ◐ Working / ● Locked | ✅ Agreed / ⚠️ Split: <function> / – Not asked |  | ⏰ if it lands late |  |

**Settled.** <decision>, <position>, locked <forum>, <date>. · ...

## Carry forward
**How many:** 1 / 2 / 3 / TBD. **Which:** Low / Mid / High.
| Candidate | Dose and exposure | Role |
| Low | | |
| Mid | | |
| High | | |
Why this number and spread: one sentence.
Project Optimus constraint: one sentence.

## Escalate, expand, stop
Escalate when ... Expand when ... Stop escalating when ...

## Gates
Gate 0 protocol, Gate 1 escalate, Gate 2 expand or stop, Gate 3 carry
forward, Gate 4 optimize, with a date on each.

Critical path: the ⏰ rows, and what the program will do about each.