PSMA CD3 T-Cell Engager Dosing Sequence for mCRPC Tolerability

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Solution Overview

Problem

Current therapies for metastatic castration-resistant prostate cancer (mCRPC) face challenges with drug resistance, limited tolerability, and lack of durable effects, necessitating a need for safe and effective combination therapies with PSMA-targeted T-cell engagers and anti-androgen compounds.

Innovation Solution

A dosing schedule is implemented where the anti-androgen compound is administered at least 3 days after the first therapeutic dose of a PSMA-targeted T-cell engaging molecule, with optional priming doses to reduce adverse events and maintain anti-tumor efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-androgen compound is administered concurrently with PSMA-targeted T-cell engaging molecule, then anti-tumor efficacy is enhanced, but safety and tolerability deteriorate due to increased adverse events and dose-limiting toxicities

Engineering Contradiction:
Improveanti-tumor efficacyVSAvoidadverse events and dose-limiting toxicities
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by administering the T-cell engaging molecule before the anti-androgen compound. Specifically, the T-cell engaging molecule is given on Day 1, followed by the anti-androgen compound on Day 8 or later, allowing T-cell priming and activation to occur before combination therapy begins, thereby reducing acute toxicities while maintaining efficacy

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements periodic action through a structured dosing schedule with specific intervals. The T-cell engaging molecule is administered every 6 weeks, and the anti-androgen compound is given at specific intervals (Day 8, Day 15, etc.), creating a rhythmic treatment pattern that allows immune system recovery and reduces cumulative toxicity

Inventive Principle:
Principle #19Periodic action

2Object-affected harmful factors

If anti-androgen compound is administered at delayed schedule (at least 3 days after T-cell engaging molecule), then safety and tolerability are improved, but anti-tumor efficacy may be compromised

Engineering Contradiction:
Improveserious adverse events and dose-limiting toxicitiesVSAvoidanti-tumor efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the timing parameter of anti-androgen administration. By setting the delay to at least 3 days (specifically Day 8 or later) and adjusting the dosing frequency, the patent finds an optimal balance where safety is improved without sacrificing anti-tumor efficacy, as demonstrated by sustained PSA responses and tumor regressions in clinical trials

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20260001962A1Combination therapy methods with t-cell engaging molecules for treatment of prostate cancer
Publication Date: 2026.01.01 AMGEN INC

AI summary

The present invention relates to treatment methods for prostate cancer using a combination of an anti-androgen compound and a T-cell engaging molecule that specifically binds to human prostate-specific membrane antigen (PSMA) and human CD3. In particular, the present invention relates to methods for treating prostate cancer, including metastatic castration-resistant prostate cancer, in a patient in need thereof comprising administering to the patient one or more cycles of an anti-androgen compound in combination with a PSMA-targeted T-cell engaging molecule, wherein administration of the first dose of the anti-androgen compound is delayed relative to administration of the first therapeutic dose of the PSMA-targeted T-cell engaging molecule in the first cycle.