J&J goes straight into phase 3 in prostate

Major biopharma players appear to be embracing a bold strategy, taking a leap from phase 1 straight into phase 3. Johnson & Johnson is the latest to follow in the footsteps of Pfizer and AbbVie, which have made similar moves in recent weeks, according to clinicaltrials.gov. 

J&J's new phase 3 trial, KLK2-comPAS, will evaluate pasritamig (JNJ-78278343), an anti-KLK2 T-cell engager, against placebo in patients with castration-resistant prostate cancer who have progressed through multiple lines of therapy, including Pluvicto. This marks J&J’s second attempt to target KLK2, following an earlier effort with the radioconjugate JNJ-6420, which was linked to four patient deaths.

The company also has a Car-T targeting KLK2, but its immediate focus has shifted to the T-cell engager, possibly because phase 1 data presented at ASCO 2025 suggested that pasritamig could offer a safer profile than a cell therapy.

In that trial pasritamig delivered a 42% PSA50 response in 33 patients receiving the go-forward regimen of 3.5mg on day 1, 18mg on day 8, 300mg intravenously on day 15 and then once every six weeks. Across the broader safety population, there was a 9% rate of cytokine release syndrome, all at grade 1.

Prostate cancer competition

But the competition in this late-line setting is intensifying. 

Janux’s JANX007, an anti-PSMA masked T-cell engager, reported a 100% PSA50 rate in 16 pre-Pluvicto patients receiving 2-9mg doses earlier this year. Safety, however, could be an issue for this asset, with Janux recently disclosing a cytokine-release syndrome mitigation strategy; previously, 6% of patients experienced grade 3 or higher CRS events, requiring intervention. 

J&J itself has a second stake in the game: ARX517, a PSMA-targeting ADC derived from the acquisition of Ambrx. In the Apex-01 trial, ARX517 achieved a PSA response in 52% of castration resistant prostate cancer patients in selected dose cohorts. On the face of it, these results look better than pasritamig, but J&J previously told ApexOnco that it was still optimising the dose of ARX517.

During the same interview, the company said it was too early for head-to-head comparisons, and that it ultimately believed that there could be room for both assets. 

Finally, Amgen’s xaluritamig is already in phase 3 trials, albeit in earlier lines of treatment. This uses yet another mechanism, being an anti-Steap1 T-cell engager. Still, data presented at ESMO 2024 showed efficacy broadly in line with ARX517 and JANX007 in late-line settings. 

Going straight from phase 1 to phase 3 will always be risky, but perhaps J&J’s decision to move fast has been spurred by the crowding in this space. The company will now need to prove that its KLK2 approach can not only deliver meaningful efficacy in a heavily treated population but also stand out in an increasingly competitive field.

Pasritamig trials 

Source: OncologyPipeline & clinicaltrials.gov.