A Phase 0 Study to Assess the Safety and Biodistribution of a Novel Radiolabeled Antibody Targeting Human Kallikrein-2 (hk2) in Subjects With Metastatic Castration-resistant Prostate Cancer.

This is an imaging trial, to develop h11B6 as a therapeutic radiopharmaceutical for men with mCRPC.
This imaging study will be conducted to confirm the safety and estimate the mass amount of antibody h11B6, and confirm in vivo tumor targeting of the antibody, using Indium-111 (111In) radiolabeled h11B6 in subjects with advanced prostate cancer. This study will also provide the dosimetric information crucial for Phase 1 therapy.

Start Date18 Sep 2019

Sponsor / Collaborator

SpectronRx

[+3]

100 Clinical Results associated with Tomopath Inc.

0 Patents (Medical) associated with Tomopath Inc.

Literatures (Medical) associated with Tomopath Inc.

01 Jun 2022·Journal of Clinical Oncology

Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.

Author: Max, Steven I ; Morris, Michael J. ; Xie, Hong ; Yu, Alex ; Avadhani, Anjali Narayan ; Pandit-Taskar, Neeta ; Sartor, A. Oliver ; Nordquist, Luke T. ; Wong, Jeffrey Y.C. ; Barata, Pedro C. ; Divgi, Chaitanya R. ; Patricia, Daniel

TPS5104 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in pharmacokinetics (PK) between 2 and 10 mg antibody mass(Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, PK, pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of 10 Feb 2022, 4 sites have been initiated and 23 patients enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.

20 Feb 2022·Journal of Clinical Oncology

Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.

Author: Max, Steven I ; Morris, Michael J. ; Xie, Hong ; Avadhani, Anjali Narayan ; Divgi, Chaitanya R ; Sartor, A. Oliver ; Russell, Mike ; Nordquist, Luke T. ; Wong, Jeffrey Y.C. ; Patricia, Daniel

TPS206 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients (pts) with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in PK between 2 and 10 mg antibody mass(Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, pharmacokinetics (PK), pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of Sep 2021, 4 sites have been initiated and 14 pts enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.

20 Feb 2021·Journal of Clinical Oncology

Pretherapeutic first-in-human targeting trial of anti-hK2 antibody h11B6: A potential molecular vector for alpha-particle radioimmunotherapy.

Author: Nyima, Tenzin ; Russell, Mike ; O' Donoghue, Joseph A. ; Morris, Michael J. ; Avadhani, Anjali Narayan ; Max, Steven ; Chetty, Dushen ; Pandit-Taskar, Neeta ; Divgi, Chaitanya R ; Wanik, Danielle

122 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has focused to date on targeting prostate specific membrane antigen, an approach associated with salivary gland toxicity and variable lesion expression. New targets are needed. Human kallikrein-2 (hK2) is overexpressed in most prostate cancer, with minimal normal tissue expression or serum secretion. Humanized monoclonal antibody (mAb) h11B6 exclusively targets hK2 in pre-clinical studies. This phase 0 study (NCT04116164) is a first-in-human trial of [111In]-DOTA-h11B6 to determine the hk2-targeting potential of h11B6. Objective: The purpose of this ongoing protocol is to characterize the biodistribution of [111In]-DOTA-h11B6 and determine a suitable mAb mass that targets mCRPC with minimal non-tumor targeting. Methods: Patients with progressive mCRPC were enrolled. A single slow bolus infusion of 2 mg [111In]-DOTA-h11B6 (nominally 185 MBq [111In]), was administered IV with or without 8 mg h11B6. Patients were observed for adverse events (AE) for at least 2 weeks. Serial gamma camera imaging including at least one SPECT/CT scan was performed up to 8 days post-administration. Serial blood samples were obtained over 2 weeks to determine serum radioactivity and h11B6 protein levels. Dosimetry for normal organs was estimated using OLINDA-EXM. Results: Results for the first 6 patients are summarized in Table. Treatment was tolerated in all patients with no AEs and no evidence of enhanced accumulation in any organ including salivary glands. Initial volume of distribution appeared confined to the vascular compartment. Slow clearance of radioactivity from the vascular compartment was observed with gradual targeting to skeletal and non-skeletal lesions in all patients. Conclusions: h11B6 is a novel mAb that targets hK2, localizes to bone and soft tissue metastases, has no significant normal tissue uptake, and spares salivary glands. An IND for a phase I therapeutic study using [225Ac] has been secured. Clinical trial information: NCT04116164. [Table: see text]

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Drug(Targets)	Indications	Global Highest Phase

111In-DOTA-h11B6 ( KLK2 )	Prostatic Cancer More	Preclinical

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