JNJ-902 is a bispecific antibody that binds to CD3 on T cells and TMEFF2-expressing tumor cells. TMEFF2 is a distinct prostate cancer lineage antigen expressed without needing androgen receptor activation and is maintained as the illness progresses. JNJ-902 demonstrated strong T cell-mediated cytotoxicity, significant pro-inflammatory responses that were exposure dependent, and strong anticancer efficacy in preclinical tests.

JNJ-902 monotherapy is being tested in this two-part, open-label phase 1 research on patients with metastatic castration-resistant prostate cancer  (mCRPC) to assess its safety, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical efficacy. The decision-making process for dose escalation and the choice of the part 2 expansion dose in Part 1 (dose escalation) was governed by a modified continual reassessment technique. JNJ-902 was originally given subcutaneously, together with a corticosteroid premedication. JNJ-902’s part 2 (dose expansion) expansion dose will be used further to assess the drug’s safety and early clinical efficacy.

JNJ-902 was administered to 73 Part 1 patient as of April 6, 2022, in 9 cohorts at escalating dosages. The tiredness (45%), decreased appetite (44%), injection site erythema (37%), anemia (33%), back pain (25%), and arthralgia (22%) were the most frequent adverse reactions (AEs) associated with therapy. Two points reported dose-limiting toxicity (all Grade 3; 1 pt, fall-required hospitalization; 1 pt, orthostatic hypotension and syncope). Four patients reported having cytokine release syndrome, which went away in 2-3 days. There were no known deaths as a result of JNJ-902. The formation of anti-drug antibodies was rare. Eight points had a PSA drop of 50% (PSA50), while 5 points had verified PR. Over the range of dosages examined, JNJ-902 shows linear PK.

When PSA50 and RECIST responses were seen, JNJ-902 displayed an acceptable safety profile at certain dosages. For patients with mCRPC, JNJ-902 is being explored as a possible treatment. The trial is now in Part 1 (dose escalation), and Part 2 (dose expansion) will start as soon as the part 2 expansion dosage is announced. An adjustment was being made to the part 2 expansion dosage selection, and dose information will be provided.

 

Reference: annalsofoncology.org/article/S0923-7534(22)03350-6/fulltext