Abstract 1367P
Background
JNJ-902 is a bispecific antibody that engages TMEFF2–expressing tumor cells and CD3 on T cells. TMEFF2 is a unique prostate cancer lineage antigen with expression independent of androgen receptor signaling and retained throughout disease progression. In preclinical studies, JNJ-902 showed exposure-dependent pro-inflammatory responses, potent T cell-mediated cytotoxicity, and robust antitumor activity.
Methods
This is a 2-part open-label, phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary clinical activity of JNJ-902 monotherapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). In Part 1 (dose escalation), a modified continual reassessment method was used to guide decision making in dose escalation and selection of the part 2 expansion dose. Subcutaneous JNJ-902 was administered with first dose given with corticosteroid premedication. Part 2 (dose expansion) will further evaluate safety and preliminary clinical activity of JNJ-902 at the part 2 expansion dose.
Results
As of April 6, 2022, 73 pts in Part 1 received at least one dose of JNJ-902 in 9 cohorts of ascending doses. Most common treatment-related AEs were fatigue (45%), decreased appetite (44%), injection site erythema (37%), anemia (33%), back pain (25%), and arthralgia (22%). Dose-limiting toxicity was reported in 2 pts (all Grade 3; 1 pt, fall-required hospitalization; 1 pt, orthostatic hypotension and syncope). Cytokine release syndrome was reported in 4 pts and resolved within 2–3 days. No deaths related to JNJ-902 were reported. Anti-drug antibody development was uncommon. PSA decline of 50% (PSA50) was observed in 8 pts and confirmed PR in 5 pts. JNJ-902 has linear PK over range of doses studied.
Conclusions
JNJ-902 presented a tolerable safety profile at certain doses when PSA50 and RECIST responses were observed. JNJ-902 is being developed as a therapeutic option for mCRPC pts. Part 1 (dose escalation) is ongoing and Part 2 (dose expansion) of study will initiate once part 2 expansion dose is declared. Selection of part 2 expansion dosage is currently being adjusted and dose information will be presented.
Clinical trial identification
NCT04397276, EudraCT 2019-004885-16.
Editorial acknowledgement
Writing assistance was provided by Paul D. Cao, PhD, of Janssen Global Services, LLC.
Legal entity responsible for the study
Janssen R&D, LLC.
Funding
Janssen R&D.
Disclosure
E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Alkermes, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech, BeiGene, MedSIR; Financial Interests, Personal, Other, Director, Clinical Research: START Madrid Group; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Ownership Interest: START, Oncoart Associated, International Cancer Consultants; Financial Interests, Institutional, Funding: Achilles; Financial Interests, Invited Speaker: EORTC IDMC; Non-Financial Interests, Invited Speaker, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) Foundation; Non-Financial Interests, Advisory Role: PsiOxus, Amcure; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis (AAA), Pfizer, Roche, Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV, Laboratoires Leurquin Mediolanum SAS, Lilly, S.A, MedImmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A. A. Avadhani: Non-Financial Interests, Institutional, Full or part-time Employment: Tempus Labs. D. Yao, V. Lin, S. Wu, P. Jaiprasart, J. Loffredo, M. Tamegnon, H. Xie: Non-Financial Interests, Institutional, Full or part-time Employment: Johnson and Johnson. All other authors have declared no conflicts of interest.