– Vepdegestrant in combination with abemaciclib demonstrated encouraging clinical activity (clinical benefit rate: 62.5%; overall response rate: 26.7%) in patients previously treated with a CDK4/6 inhibitor –
– Safety and tolerability of the combination is generally consistent with the profile of abemaciclib and what has been observed in other clinical trials of vepdegestrant; no significant drug-drug interaction was observed between vepdegestrant and abemaciclib –
– Recommended Phase 2 dose identified as 200 mg QD vepdegestrant and 150 mg BID abemaciclib –
NEW HAVEN, CT and NEW YORK, NY, USA I December 10, 2024 I Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. These data will be presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.
Preliminary results from 16 patients in the Phase 1b sub-study demonstrated a tolerable safety profile for the combination of abemaciclib 150 mg twice daily (BID) with the recommended Phase 3 monotherapy dose of vepdegestrant (200mg once daily; QD). An encouraging clinical benefit rate of 62.5% was observed among patients with both mutant ESR1 and wild-type ESR1 disease who had all been previously treated with a CDK4/6 inhibitor.
Pharmacokinetic data demonstrated no significant drug-drug interaction between vepdegestrant and abemaciclib and no clinically meaningful effect on abemaciclib exposure was observed. In addition to tolerability, the results demonstrated a safety profile consistent with both the known properties of abemaciclib and observed data in other clinical trials for vepdegestrant. These findings support the ongoing Phase 2 portion of the study, which is evaluating full dose abemaciclib (150mg BID) in combination with vepdegestrant (200 mg QD) in post-CDK4/6 advanced breast cancer.
“The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “These data further reinforce our belief that vepdegestrant can be used in multiple combination regimens across the metastatic breast cancer setting and has the potential to become a best-in-class backbone ER therapy. We are pleased to continue in the Phase 2 portion of the study evaluating the standard starting dose of abemaciclib in combination with vepdegestrant.”
“With vepdegestrant, we aim to develop a novel agent that has the potential to become a new backbone endocrine therapy in ER+ metastatic breast cancer,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “We are pleased to see these initial results, which complement previously reported data demonstrating the potential of combination therapy with vepdegestrant to address unmet needs for patients.”
Additional detail on the TACTIVE-U poster presentation at SABCS follows below:
Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results
Date: Thursday, December 12, 2024
Time: 5:30 – 7:00 p.m. CDT
Poster: P4-12-03
Key findings included in the poster (data cut-off: August 30, 2024):
- 100% of patients had prior treatment with a CDK4/6 inhibitor.
- Tolerability is generally consistent with the profile of abemaciclib and with results previously observed in other clinical trials of vepdegestrant. The most common any grade treatment-emergent adverse events (TEAE) were diarrhea, nausea and fatigue. There were no dose-limiting toxicities and no grade 4 or 5 TEAEs.
- There was no significant drug-drug interaction, and data reflected vepdegestrant has no clinically meaningful effect on abemaciclib exposure.
- Encouraging preliminary antitumor activity is observed with a clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 62.5% in all CBR-eligible patients (10/16), 62.5% in patients with mutant ESR1 (5/8), and 62.5% in patients with wild-type ESR1 (5/8).
- The objective response rate (ORR) in evaluable patients was 26.7% overall (4/15), 37.5% in patients with mutant ESR1 (3/8), and 14% in patients with wild-type ESR1 (1/7).
- Five patients remained on study treatment as of the August 30, 2024 data cut-off.
Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial, which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).
About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.
In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.
The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
About Arvinas
Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis TArgeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
SOURCE: Pfizer
Post Views: 1,149
– Vepdegestrant in combination with abemaciclib demonstrated encouraging clinical activity (clinical benefit rate: 62.5%; overall response rate: 26.7%) in patients previously treated with a CDK4/6 inhibitor –
– Safety and tolerability of the combination is generally consistent with the profile of abemaciclib and what has been observed in other clinical trials of vepdegestrant; no significant drug-drug interaction was observed between vepdegestrant and abemaciclib –
– Recommended Phase 2 dose identified as 200 mg QD vepdegestrant and 150 mg BID abemaciclib –
NEW HAVEN, CT and NEW YORK, NY, USA I December 10, 2024 I Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. These data will be presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.
Preliminary results from 16 patients in the Phase 1b sub-study demonstrated a tolerable safety profile for the combination of abemaciclib 150 mg twice daily (BID) with the recommended Phase 3 monotherapy dose of vepdegestrant (200mg once daily; QD). An encouraging clinical benefit rate of 62.5% was observed among patients with both mutant ESR1 and wild-type ESR1 disease who had all been previously treated with a CDK4/6 inhibitor.
Pharmacokinetic data demonstrated no significant drug-drug interaction between vepdegestrant and abemaciclib and no clinically meaningful effect on abemaciclib exposure was observed. In addition to tolerability, the results demonstrated a safety profile consistent with both the known properties of abemaciclib and observed data in other clinical trials for vepdegestrant. These findings support the ongoing Phase 2 portion of the study, which is evaluating full dose abemaciclib (150mg BID) in combination with vepdegestrant (200 mg QD) in post-CDK4/6 advanced breast cancer.
“The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “These data further reinforce our belief that vepdegestrant can be used in multiple combination regimens across the metastatic breast cancer setting and has the potential to become a best-in-class backbone ER therapy. We are pleased to continue in the Phase 2 portion of the study evaluating the standard starting dose of abemaciclib in combination with vepdegestrant.”
“With vepdegestrant, we aim to develop a novel agent that has the potential to become a new backbone endocrine therapy in ER+ metastatic breast cancer,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “We are pleased to see these initial results, which complement previously reported data demonstrating the potential of combination therapy with vepdegestrant to address unmet needs for patients.”
Additional detail on the TACTIVE-U poster presentation at SABCS follows below:
Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results
Date: Thursday, December 12, 2024
Time: 5:30 – 7:00 p.m. CDT
Poster: P4-12-03
Key findings included in the poster (data cut-off: August 30, 2024):
- 100% of patients had prior treatment with a CDK4/6 inhibitor.
- Tolerability is generally consistent with the profile of abemaciclib and with results previously observed in other clinical trials of vepdegestrant. The most common any grade treatment-emergent adverse events (TEAE) were diarrhea, nausea and fatigue. There were no dose-limiting toxicities and no grade 4 or 5 TEAEs.
- There was no significant drug-drug interaction, and data reflected vepdegestrant has no clinically meaningful effect on abemaciclib exposure.
- Encouraging preliminary antitumor activity is observed with a clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 62.5% in all CBR-eligible patients (10/16), 62.5% in patients with mutant ESR1 (5/8), and 62.5% in patients with wild-type ESR1 (5/8).
- The objective response rate (ORR) in evaluable patients was 26.7% overall (4/15), 37.5% in patients with mutant ESR1 (3/8), and 14% in patients with wild-type ESR1 (1/7).
- Five patients remained on study treatment as of the August 30, 2024 data cut-off.
Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial, which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).
About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.
In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.
The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
About Arvinas
Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis TArgeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
SOURCE: Pfizer
Post Views: 1,149
