JNJ-8177 / J&J - LARVOL DELTA

GenSci143, a Novel B7-H3 × PSMA Bispecific Antibody-Drug Conjugate (BsADC), Demonstrates Broad-Spectrum Preclinical Antitumor Efficacy with a Favorable Safety Profile (AACR-NCI-EORTC 2025) - "Clinical limitations of single-target agents include restricted efficacy in mCRPC monotherapy (e.g., DS-7300a [anti-B7-H3 ADC] and ARX517 [anti-PSMA ADC]), often attributed to tumor heterogeneity and variable target expression...Combination potential with enzalutamide (endocrine therapy) was evaluated in a PCa PDX model...The association with the SLFN11 biomarker may further optimize patient stratification. These results position GenSci143 as a promising therapeutic modality with enhanced efficacy and expanded patient coverage potential for mCRPC and beyond."

Preclinical • Castration-Resistant Prostate Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD276 • FOLH1 • SLFN11 • TOP1

Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - P3 | "Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 (dual PSMA/STEAP1-targeted), and DXC008 (dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, the B7-H3-targeted ADC ifinatamab deruxtecan has initiated..."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2 • SLC44A4 • SLC4A4 • STEAP1

A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov) - P1 | N=110 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of JNJ-78278343 in Combination With JNJ-95298177 for Treatment of Prostate Cancer (clinicaltrials.gov) - P1 | N=110 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=253 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Sep 2026 ➔ Dec 2028 | Trial primary completion date: May 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

GenSci143, a novel B7-H3×PSMA bispecific and potential best-in-class ADC, for the treatment of metastatic castration-resistant prostate cancer (AACR 2025) - "In vivo anti-tumor activity of GenSci143 was assessed in CDX models of PCa and compared to that of the DS-7300 and ARX517 analogs. B7-H3 and PSMA were highly co-expressed in PCa tissues (N=102), lending strong support to our dual-targeting therapeutic approach for mCRPC. These results suggest that GenSci143 has the potential to become an effective therapeutic option for mCRPC patients and support its further evaluation in IND-enabling studies."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=253 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Dec 2028 ➔ Sep 2026

Monotherapy • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

APEX-01: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=352 | Recruiting | Sponsor: Ambrx, Inc. | N=262 ➔ 352 | Trial completion date: Mar 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ May 2026

Combination therapy • Enrollment change • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • FOLH1

Preclinical Characterization of ARX517, a Site-specific Stable PSMA-Targeted Antibody Drug Conjugate for Treatment of Metastatic Castration-Resistant Prostate Cancer. (PubMed, Mol Cancer Ther) - P1 | "ARX517 exhibited a long terminal half-life and high serum exposure in mice, and dose-dependent anti-tumor activity in both enzalutamide-sensitive and -resistant CDX and PDX prostate cancer models. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a Phase 1 clinical trial ([NCT04662580])."

Journal • Metastases • Preclinical • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

APEX-01: ARX517 in Subjects With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=262 | Recruiting | Sponsor: Ambrx, Inc. | Phase classification: P1/2 ➔ P1

Metastases • Phase classification • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Dr Shen on the Utility of ARX517 in mCRPC (OncLive) - P1/2 | N=222 | APEX-01 (NCT04662580) | Sponsor: Ambrx, Inc. | "Early data from this trial demonstrated both the efficacy and safety of ARX517 in a patient population that had undergone extensive prior treatments, Shen explains. Notably, substantial reductions in prostate-specific antigen (PSA) levels were observed with increasing doses of ARX517, even in patients who had previously received PSMA-targeted radionuclide therapies, he notes....This study highlights that at putative therapeutic doses of 2 mg/kg or higher, 52% of patients achieved a PSA reduction of 50%, he expands. These early efficacy results, particularly in terms of PSA reduction, are promising, Shen elucidates."

P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer

Johnson & Johnson Completes Acquisition of Ambrx (Businesswire) - "Johnson & Johnson...announced today it has successfully completed the acquisition of Ambrx Biopharma, Inc...in an all-cash merger transaction for a total equity value of approximately $2.0 billion, or $1.9 billion net of estimated cash acquired, as announced on January 8, 2024...'We’re pleased to welcome Ambrx’s talented scientific team and proprietary ADC platform to Johnson & Johnson. We look forward to continuing the development of ARX517, which represents a potential first- and best-in-class PSMA-targeting ADC for the treatment of metastatic castration-resistant prostate cancer.'....The acquisition presents a distinct opportunity for Johnson & Johnson to design, develop and commercialize targeted oncology therapeutics."

M&A • Breast Cancer • Castration-Resistant Prostate Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • HER2 Breast Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Johnson & Johnson to Acquire Ambrx, Advancing Next Generation Antibody Drug Conjugates to Transform the Treatment of Cancer (Businesswire) - "Johnson & Johnson...announced today it has entered into a definitive agreement to acquire Ambrx Biopharma, Inc., or Ambrx...in an all-cash merger transaction for a total equity value of approximately $2.0 billion, or $1.9 billion net of estimated cash acquired...Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety of its candidate therapeutics in multiple cancer indications, including ARX517, its proprietary ADC targeting PSMA for metastatic castration-resistant prostate cancer (mCRPC); ARX788, its proprietary ADC targeting human epidermal growth factor receptor 2 (HER2) for metastatic HER2+ breast cancer; and ARX305, its proprietary ADC targeting CD-70 for renal cell carcinoma....Building on a legacy of innovation in oncology and in prostate cancer, J&J scientists intend to work with Ambrx researchers, accelerating the Phase 1/2 APEX-01 study (NCT04662580) of ARX517 in advanced prostate cancer..."

M&A • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Kidney Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

APEX-01: ARX517 as Monotherapy and in Combination Regimens in Subjects With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=222 | Recruiting | Sponsor: Ambrx, Inc.

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Ambrx Provides Update On APEX-01, an On-Going Phase 1 / 2 Dose Escalation Study Evaluating ARX517, a Proprietary PSMA-Targeting ADC, in Metastatic Castration-Resistant Prostate Cancer (GlobeNewswire) - P1/2 | N=222 | APEX-01 (NCT04662580) | Sponsor: Ambrx, Inc. | "Following the completion of the 21-day DLT observation period from APEX-01 dose escalation Cohort 9 (3.4 mg/kg), no DLTs or SAEs were observed. Two of the three patients in Cohort 9 had a rapid PSA reduction of 91% and 33% at the first PSA assessment at three weeks post-treatment and following only one dose of ARX517....All expansion cohorts, Cohort 4 (1.4 mg/kg at n=23), Cohort 6 (2.0 mg/kg at n=23), and Cohort 8 (2.88 mg/kg at n=20) are now fully enrolled....'The high interest in our PSMA-targeting ADC and pace of enrollment in the APEX-01 study has been outstanding and based on this we are anticipating to reach a recommended phase 2 dose by early next year.'"

P1/2 data • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

APEX-01: ARX517 as Monotherapy and in Combination Regimens in Subjects With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=222 | Recruiting | Sponsor: Ambrx, Inc. | N=150 ➔ 222

Enrollment change • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

ARX517: A next generation anti-PSMA antibody drug conjugate (ADC) demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 phase I clinical trial (APEX-01) (ESMO 2023) - P1/2 | "Conclusions ARX517 is the first anti-PSMA ADC tested in the clinic to demonstrate notable stability and a long terminal half-life. These attributes enable continuous drug delivery throughout the dosing cycle to potentially improve efficacy and minimize toxicity due to premature payload release, indicating a clear and favorable therapeutic index."

Clinical • P1 data • PK/PD data • Oncology

APEX-01: First-in-human phase I/II study of ARX517 an anti- prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2023) - P1/2 | "Table: 1804P PSA and ctDNA decline, confirmed responses, DLTs, and Grade 3/4/5 TRAEs by dose level Conclusions ARX517 treatment resulted in PSA declines and RECIST v1.1 responses without treatment-related SAEs. Dose expansion has begun, additional safety, PD, efficacy, and PSMA PET data will be presented."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Evaluation of ARX517: A next-generation anti-PSMA antibody drug conjugate for prostate cancer treatment, in preclinical enzalutamide-resistant and enzalutamide-sensitive pharmacology models and in toxicology models (ESMO 2023) - P1/2 | "Conclusions In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on strong preclinical data and recent clinical validation of PSMA targeting, ARX517 is being evaluated in a phase 1/2 clinical trial (NCT04662580)."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Ambrx Announces ARX517, a PSMA-Targeted ADC, Demonstrates a Promising 52% PSA50 (≥50% Reduction) and a Highly Differentiated Safety and PK Profile in Patients with mCRPC, who Progressed on Multiple FDA-Approved Treatments (GlobeNewswire) - P1/2 | N=150 | APEX-01 (NCT04662580) | Sponsor: Ambrx, Inc. | "Ambrx Biopharma...announced that in biomarker unselected patients ARX517 monotherapy demonstrated a strong antibody-drug conjugate (ADC) safety profile at all doses tested with promising early efficacy signals that included PSA50 declines, ctDNA reductions, and RECIST v1.1 tumor response. The ESMO clinical posters present updated safety, efficacy and PK data from Ambrx’s on-going trial, APEX-01....Multiple efficacy endpoints demonstrate consistent and promising anti-cancer activity at therapeutic doses of 2.0 - 2.88 mg/kg (Cohorts 6-8) in heavily pretreated patients (median of 4 and maximum of 13 prior lines of therapy)....Pharmacokinetics (PK) data demonstrates strong ADC stability....Full-loaded DAR2 ARX517 does not prematurely release its payload thus maximizing delivery of cytotoxic payload to PSMA-expressing cancer cells."

P1 data • PK/PD data • Prostate Cancer

Dr Pachynski on the Ongoing Investigation of ARX517 in Advanced Solid Tumors (OncLive) - "Russell Pachynski, MD...discusses the ongoing investigation of ARX517 in patients with advanced solid tumors, including prostate cancer, in the phase 1/2 APEX-01 trial (NCT04662580)....Overall, early results demonstrate the potential efficacy of ARX517 in reducing PSA levels and its tolerability in patients with metastatic prostate cancer, Pachynski concludes. The dose-escalation study is ongoing and continues to enroll patients."

Video

Ambrx Provides Safety and Efficacy Data from Ongoing Phase 1/2 APEX-01 Trial of ARX517 in mCRPC at ESMO Congress (GlobeNewswire) - P1/2 | N=150 | APEX-01 (NCT04662580) | Sponsor: Ambrx, Inc. | "≥50% PSA reduction observed across putative therapeutic dose levels ≥2.0 mg/kg – 3 of 3 in Cohort 6 (2.0 mg/kg), 2 of 3 in Cohort 7 (2.4 mg/kg) and 2 of 3 in Cohort 8 (2.88 mg/kg); No drug-related severe adverse events (SAEs) and no dose limiting toxicities (DLTs) observed in any cohort; Pharmacokinetic (PK) data indicated strong ADC stability preventing premature release of anticancer payload; Ambrx to host a live event / webcast to discuss additional data presented at ESMO on Sunday, October 22, 2023, at 8 p.m. CEST / 2 p.m. ET."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Ambrx to Host KOL Event Discussing ARX517 Data Presented at ESMO Congress 2023 (GlobeNewswire) - "Ambrx Biopharma Inc...today announced that it will host an in-person key opinion leader (KOL) event during the European Society for Medical Oncology (ESMO) Congress 2023. The event will take place on Sunday, October 22, 2023 from 8:00pm – 10:00pm CEST (2:00pm – 4:00pm ET) at the Santo Mauro Hotel in Madrid, Spain. Discussions will feature preliminary safety, efficacy, and pharmacokinetic (PK) data from APEX-01 (NCT04662580), a first-in-human study evaluating ARX517 in prostate cancer patients, which will be presented for the first time at ESMO 2023."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Ambrx to Host KOL Event Discussing ARX517 Data Presented at ESMO Congress 2023 (GlobeNewswire) - "The event will showcase presentations from prostate cancer experts, Scott T. Tagawa, MD, MS, FACP, FASCO...."

Live event

Ambrx to Present at the Baird and Morgan Stanley Global Healthcare Conferences (GlobeNewswire) - "Ambrx Biopharma Inc...announced that Daniel J. O’Connor, Chief Executive Officer and President of Ambrx, will present a corporate overview and participate in one-on-one meetings at the Baird Global Healthcare Conference and the Morgan Stanley 21st Annual Global Healthcare Conference, both being held in New York, NY. The presentations will focus on the status of Ambrx’s lead clinical candidates, ARX788 and ARX517."

Clinical data • Oncology