luxdegalutamide (ARV-766) / Arvinas, Novartis - LARVOL DELTA

An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01) (clinicaltrials.gov) - P1/2 | N=188 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

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

An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01) (clinicaltrials.gov) - P1/2 | N=188 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase I Study of JSB462 (Luxdegalutamide) in Japanese Patients With Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

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

A Study of JSB462 (Luxdegalutamide) Plus Lutetium (177Lu) Vipivotide Tetraxetan in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

An Open-label Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

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

An Open-label Study of JSB462 (Luxdegalutamide) in Combination With Abiraterone in Adult Male Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Discovery of GLR203701, a highly potent AR PROTAC with favorable PK profile and optimized tissue distribution characteristic (AACR 2025) - "Phase 1 dose escalation trial showed systemic exposure of ARV-766 reached maximum at 320 mg/day in humans. Taking the high exposure level and good bioavailability, GLR203701 is expected to generate a board therapeutic window. These preclinical data support the clinical development of GLR203701 for the treatment of mCRPC."

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

ARV-766-mCRPC-101: A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=152 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=220 ➔ 152 | Trial completion date: Jun 2026 ➔ May 2027 | Trial primary completion date: Dec 2025 ➔ May 2027

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

Developing novel AR mutant prostate cancer models for CRPC related drug discovery (EORTC-NCI-AACR 2024) - "The modified cell line exhibited resistance to enzalutamide but remained sensitive to target protein degraders (TPDs), such as ARV-766, both in vitro and in vivo...Consistent with the preclinical studies previously reported, AR degraders (ARV-110 and ARV-766) are able to degrade these two clinically relevant mutant AR proteins and induce cell death. In summary, we present three engineered LNCaP prostate cancer models with certain AR hot spot mutations, T878A/F877L, T878S and T878A/H875Y. Their differential responses to AR antagonists or new drug modalities not only provide indications for the understanding of hormonal treatment resistance mechanism but also have implications for clinical utilization."

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

Arvinas Reports Second Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Research and development expenses were $93.7 million for the quarter ended June 30, 2024, as compared with $103.4 million for the quarter ended June 30, 2023. The decrease in research and development expenses of $9.7 million for the quarter was primarily due to decreases in expenses related to our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer) of $6.6 million and our platform and exploratory programs of $5.7 million, partially offset by an increase in our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $2.6 million. Revenues were $76.5 million for the quarter ended June 30, 2024, as compared with $54.5 million for the quarter ended June 30, 2023."

Commercial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology

PROTAC'ing the androgen receptor and other emerging therapeutics in prostate cancer. (PubMed, Expert Rev Anticancer Ther) - "PROTACs, DAARIs, and anitens represent novel and promising AR-targeting therapeutics that may become an important part of prostate cancer treatment in the future. Elucidating mechanisms of resistance, including ability of these agents to target full length AR, may yield further insights into maximal therapeutic efficacy aimed at silencing AR signaling."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR

ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study. (ASCO 2024) - P1/2 | "In this phase 1/2 study of pretreated patients with mCRPC, ARV-766 was well tolerated and showed promising clinical activity in those with tumors harboring AR LBD mutations. ARV-766 warrants further development in advanced prostate cancer."

Metastases • P1/2 data • Alopecia • Fatigue • Genito-urinary Cancer • Immunology • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR

ARV-766 shows promising efficacy and tolerability in mCRPC (Urology Times) - P1/2 | N=220 | NCT05067140 | Sponsor: Arvinas Androgen Receptor, Inc. | "ARV-766, an investigational proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, was well tolerated and showed clinical activity in pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), according to data presented during the 2024 ASCO Annual Meeting....Patients must have experienced disease progression following at least 2 prior systemic therapies including 1 ARPI and be actively undergoing androgen deprivation therapy....Pharmacokinetics of ARV-766 monotherapy indicated there were dose-dependent increases in ARV-766 exposure up to 320 mg daily in the phase 1 portion, with exposure accumulating from approximately 5- to 8-fold at steady state. The mean area under the curve from 0 to 24 hours at steady state at the 100 mg and 300 mg doses exceeded the minimal preclinical efficacious thresholds, leading these to be selected as the recommended phase 2 doses."

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

PROTACs targeting androgen receptor signaling: potential therapeutic agents for castration-resistant prostate cancer. (PubMed, Pharmacol Res) - "This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Sexual Disorders • Solid Tumor • Targeted Protein Degradation

Arvinas Announces Upcoming Presentations at the 2024 American Society of Clinical Oncology Annual Congress (GlobeNewswire) - "Arvinas, Inc...today announced that two abstracts, including one for ARV-766 in prostate cancer and one for TACTIVE-K, a Phase 1b/2 clinical trial with vepdegestrant...in combination with Pfizer’s atirmociclib (PF-07220060)...were accepted for presentation at the 2024 American Society of Clinical Oncology Annual Congress held May 31 to June 4, 2024, in Chicago, IL."

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

ARV-766, a PROTAC androgen receptor (AR) degrader, combined with abiraterone in novel hormonal agent (NHA)-naïve metastatic prostate cancer: phase 1 cohort (part C) of a phase 1/2 study (AUA 2024) - P1/2 | "ARV-766 monotherapy was well tolerated in NHA-exposed pts with mCRPC; analyses of anti-tumor activity in parts A & B are ongoing. Part C of the study will assess the safety, tolerability, and DDI of combination ARV-766/abiraterone treatment in NHA-naïve mCRPC or mCSPC."

Metastases • P1/2 data • Alopecia • Fatigue • Genito-urinary Cancer • Immunology • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR

Arvinas Reports First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus atirmociclib, Pfizer’s novel CDK4 inhibitor....Initiate dosing in first-in-human Phase 1 clinical trial in B-cell lymphomas with PROTAC BCL6 degrader ARV-393 (2Q 2024)....The decrease in research and development expenses of $11.0 million for the quarter was primarily due to a decrease in expenses related to our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $8.2 million, our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement) of $2.3 million and our platform and exploratory programs of $0.5 million."

Commercial • Regulatory • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Arvinas Enters into a Transaction with Novartis, including a Global License Agreement for the Development and Commercialization of PROTAC Androgen Receptor (AR) Protein Degrader ARV-766 for the Treatment of Prostate Cancer (GlobeNewswire) - "Arvinas, Inc...today announced it has entered into an exclusive strategic license agreement with Novartis...for the worldwide development and commercialization of ARV-766, Arvinas’ second generation PROTAC androgen receptor (AR) degrader for patients with prostate cancer. The transaction also includes an asset purchase agreement for the sale of Arvinas’ preclinical AR-V7 program to Novartis...Under the terms of the transaction agreements, Novartis will be responsible for worldwide clinical development and commercialization of ARV-766 and will have all research, development, manufacturing, and commercialization rights with respect to the preclinical AR-V7 program. Arvinas will receive an upfront payment in the aggregate amount of $150.0 million. Under the License Agreement, Arvinas is eligible to receive additional development, regulatory, and commercial milestones of up to $1.01 billion, as well as tiered royalties for ARV-766."

Licensing / partnership • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Arvinas Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate first-in-human Phase 1 clinical trial in B-cell lymphomas with BCL6 targeting PROTAC ARV-393 (1H 2024)....The increase in research and development expenses of $64.7 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $1.1 million, our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $22.0 million and our ER program of $41.6 million, which includes the cost sharing of vepdegestrant (ARV-471) under the Vepdegestrant (ARV-471) Collaboration Agreement."

Commercial • New P1 trial • Hematological Malignancies • Lymphoma • Oncology

Arvinas Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus Pfizer’s novel CDK4 inhibitor (PF-07220060). ARV-766: Continue enrollment of Phase 2 dose expansion study with ARV-766, with progression free survival data anticipated in mid-2024. Continue enrollment of Phase 1b/2 dose escalation trial with ARV-766 in combination with abiraterone in patients who have not previously received novel hormonal agents. Initiate discussions with regulatory authorities for a planned Phase 3 clinical trial with ARV-766 in mCRPC (2Q 2024)."

Enrollment status • P2 data • Regulatory • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Arvinas Androgen Receptor, Inc. | N=150 ➔ 220 | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment change • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Arvinas Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology)...Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023....The increase in research and development expenses of $8.4 million for the quarter was primarily due to increases our AR program of $5.2 million, which includes ARV-766 and bavdegalutamide, and our ER program of $6.2 million, which is net of the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement, offset by a decrease in our platform and exploratory programs of $3.0 million."

Commercial • IND • Oncology

Arvinas Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Continue enrollment of Phase 2 dose expansion study with ARV-766, with progression free survival data anticipated in 2024. Initiate a Phase 1b/2 dose escalation trial with ARV-766 in combination with abiraterone in patients who have not previously received novel hormonal agents (4Q 2023). Initiate discussions with regulatory authorities for a planned Phase 3 trial with ARV-766 in mCRPC (2Q 2024)."

New P1/2 trial • New P3 trial • P2 data • Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Potential of Arvinas’ PROTAC AR Degraders Reinforced by 11.1 months rPFS with Bavdegalutamide and Updated Positive Interim Data from Second Generation ARV-766 in mCRPC (GlobeNewswire) - P1/2 | N=150 | NCT05067140 | Sponsor: Arvinas Androgen Receptor, Inc. | "Data from an updated analysis of the ongoing Phase 1/2 clinical trial demonstrate broad efficacy and excellent tolerability in mCRPC patients with tumors harboring AR LBD mutations, including AR L702H: PSA50 of 41% in patients with tumors harboring any AR LBD mutation, and a PSA50 of 50% in patients with any tumor harboring an AR L702H mutation; ARV-766 was well-tolerated, with no grade ≥ 4 TRAEs. The most common TRAEs were grade 1 or 2 and included fatigue (29%), nausea (14%), vomiting (11%), and diarrhea (11%)....Arvinas will prioritize the initiation of a Phase 3 clinical trial with ARV-766 in mCRPC instead of the previously planned Phase 3 clinical trial for bavdegalutamide. The Company will initiate discussions with regulatory authorities by 2Q 2024."

New P3 trial • P1/2 data • Regulatory • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Arvinas Reports Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate a Phase 1b/2 dose escalation trial with ARV-766 in combination with abiraterone in patients who have not previously received novel hormonal agents (2H 2023)."

New P1/2 trial • Oncology • Solid Tumor