New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

In continuation of my update on Palbociclib,

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

“All living cells undergo cell division and palbociclib’s unique capacity to halt the cell division process (also known as the ‘cell cycle’) therefore has potentially broad applicability,” said the study’s lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn’s Perelman School of Medicine and ACC. “Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers.” For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells. 

“This drug has minor effects on normal cells other than neutrophils (white blood cells),” said the study’s senior author, Peter J. O’Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better.”

In addition to inhibiting the cell cycle, palbociclib has been shown, for example, to alter several recently described non–cell cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.

Assessing 130 relevant publications in the literature, as well as interpreting their own continuing studies, the all-Penn team found that in addition to its safety and effectiveness in fighting certain types of breast cancer, early trials of palbociclib have shown promise of effectiveness in cases of lymphoma, sarcoma, and teratoma, tumors that while rare, often afflict younger patients.

A phase 2 trial showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in one complete response and two partial responses. Although, median progression-free survival was four months, five patients had progression-free survival greater than one year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66 percent at 12 weeks.

Also, combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

Palbociclib and paclitaxel combination shrinks tumors in patient with ER positive breast cancer

Combining the new breast cancer drug palbociclib with paclitaxel (Taxol) shrank tumors in nearly half of patient with estrogen-receptor (ER) positive breast cancer, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The results will be presented Saturday at the 2015 San Antonio Breast Cancer Symposium (Abstract P6-13-08). A second study (Abstract P4-13-04), to be presented Friday provides new clues to how breast cancer develops resistance to the palbociclib, a common occurrence among many patients who take the drug.

"Results of the first study found that palbociclib and paclitaxel can be safely combined on an alternating dosing schedule," said Angela DeMichele, MD, MSCE, the Alan and Jill Miller Associate Professor in Breast Cancer Excellence in Penn's Abramson Cancer Center, and senior author on the study. "The high response rate we saw suggests this combination may hold benefits for patients over paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted."

A Complementary Therapy

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which help drive cell division and are upregulated in most cancers. The researchers suspected that palbociclib's unique mechanism of action may make it a good partner for other breast cancer drugs such as paclitaxel, which kills dividing cells at a certain point in the cell division process (also known as the "cell cycle"). Palbociclib effectively halts the cell cycle before that point, and thus in principle can synchronize cancer cells in a way that makes them more vulnerable to a closely following dose of paclitaxel.

Palbociclib and paclitaxel combination shrinks tumors in patient with ER positive breast cancer

Investigational drug abemaciclib shows durable clinical activity for variety of cancer types

In continuation of my  updates on palbociclib (Ibrance)  and letrozole

Bottom Line: The investigational anticancer therapeutic abemaciclib, which targets CDK4 and CDK6, showed durable clinical activity when given as continuous single-agent therapy to patients with a variety of cancer types, including breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, and melanoma, according to results from a phase I clinical trial.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research.

Senior authors: Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas, and Geoffrey I. Shapiro, MD, PhD, director of the Early Drug Development Center at the Dana-Farber Cancer Institute in Boston.

Background: In February 2015, the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor palbociclib (Ibrance) for use in combination with the aromatase inhibitor letrozole for treating postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer.

  letrozole  palbociclib

The oral CDK4/6 inhibitor abemaciclib is a very different molecule from palbociclib, with distinct attributes that contribute to its discrete therapeutic effects, in particular, its single-agent activity, according to Shapiro. For example, abemaciclib has greater selectivity for CDK4 compared with palbociclib, which may explain why it does not affect white blood cell counts as severely, allowing it to be taken on a continuous schedule without treatment holidays, he said. Abemaciclib also penetrates the central nervous system, whereas palbociclib does not, raising the possibility that it could be used to treat primary or metastatic brain tumors, he added.

 abemaciclib

How the Study Was Conducted and Results: Patnaik, Shapiro, and colleagues enrolled 225 patients with a variety of types of advanced cancer in the phase I clinical trial designed to evaluate the safety and preliminary efficacy of abemaciclib. In the dose escalation phase, the researchers determined that the maximum tolerated dose was 200 milligrams (mg) every 12 hours; the dose-limiting toxicity was grade 3 fatigue.

In the expansion phase, single-agent abemaciclib was administered to 47 patients with breast cancer, 68 with NSCLC, 17 with glioblastoma, 26 with melanoma, and 15 with colorectal cancer. Among these patients, the most common treatment-related adverse events were fatigue, diarrhea, nausea, vomiting, anorexia, weight loss, kidney dysfunction, and decreased red and white blood cell counts.

Radiographic responses were observed for some patients with breast cancer, NSCLC, and melanoma. Among the 36 patients with hormone receptor-positive breast cancer, 11 had a partial response, with four of the 11 responders having continued prior endocrine therapy, and an additional 18 patients had stable disease. Among the 68 patients with NSCLC, two had a partial response and 31 had stable disease; one patient who had a partial response and 12 who had stable disease were known to have KRAS-mutant NSCLC. Among the 26 patients with melanoma, one had a partial response and six had stable disease. Three of the 17 patients with glioblastoma had stable disease, with two of them continuing to receive treatment without disease progression for 19 and 23 cycles, respectively.

Author Comment: "These data show that abemaciclib is an oral drug that can be taken on a continuous schedule and achieve durable clinical activity against multiple tumors including breast and lung cancers," said Shapiro.

"The results of the trial supported the FDA decision to grant breakthrough therapy designation to abemaciclib (previously known as LY2835219) for patients with refractory hormone receptor-positive advanced or metastatic breast cancer," added Patnaik.

Limitations: Patnaik explained that because this study included 225 patients with different types of cancer, confirmatory clinical trials in specific patient populations are necessary to precisely define the role of abemaciclib in cancer care. Multiple clinical trials have already been initiated to evaluate abemaciclib as a treatment for certain groups of patients with breast cancer and NSCLC, as well as children with primary brain tumors and adults with brain metastases, she noted.

New oral breast cancer drug has potential to combat other types of cancer

In continuation of my update on Palbociclib

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

"All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process (also known as the 'cell cycle') therefore has potentially broad applicability," said the study's lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn's Perelman School of Medicine and ACC. "Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers." For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells.

"This drug has minor effects on normal cells other than neutrophils (white blood cells)," said the study's senior author, Peter J. O'Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. "In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better."

New oral breast cancer drug has potential to combat other types of cancer

Palbociclib extends progression-free survival in advanced breast cancer patients

In continuation of my update on Palbociclib

Palbociclib, an investigational oral medication that works by blocking molecules responsible for cancer cell growth, is well tolerated and extends progression-free survival (PFS) in newly diagnosed, advanced breast cancer patients, including those whose disease has stopped responding to traditional endocrine treatments. Results of the phase II study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania , were published this month in Clinical Cancer Research. Earlier phase I results by researchers at Penn Medicine contributed to the development of palbociclib, which was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic breast cancer patients just beginning to undergo endocrine therapy.

"The FDA approval has expanded treatments options for many metastatic breast cancer patients, but these new results are showing how effective the drug can also be for breast cancer patients who have already tried endocrine therapies and may be running out of options," said lead investigator Angela DeMichele, MD, MSCE , associate professor in the division of Hematology/Oncology and Epidemiology and co-leader of the Breast Cancer Research Program at the Abramson Cancer Center. "Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy."

The newly-published phase II trial primarily sought to evaluate disease response and control, while monitoring for the presence of side effects such as neutropenia, an abnormally low white blood cell count. Patients enrolled in the trial had previously undergone several prior chemotherapy and hormonal regimens for metastatic disease. Palboclib was administered once daily for 21 days each month.

Overall, researchers noted a median PFS, the time before a tumor worsens or the patient dies, of 3.7 months for patients taking the drug. However, patients with hormone receptor-positive (HR+) breast cancer -where the breast cancer cells depend on the hormones estrogen and progesterone to grow - had significantly longer PFS (5.1 months) compared to that of the HR-negative group (84 percent and 11 percent of the enrolled population, respectively). And those who had previously progressed through at least two rounds of hormonal therapy saw significantly greater benefits, suggesting substantial activity in the setting of acquired endocrine resistance.

Palbociclib extends progression-free survival in advanced breast cancer patients

Pfizer Announces Submission of Palbociclib New Drug Application to the FDA

Pfizer Inc. today announced it has completed the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for palbociclib. This NDA requests FDA approval of palbociclib, in combination with letrozole, for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

Pfizer Announces Submission of Palbociclib New Drug Application to the FDA

Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial.

FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

In continuation of my update on palbociclib

The U.S. Food and Drug Administration today granted accelerated approval to Ibrance (palbociclib) to treat advanced (metastatic) breast cancer.

Breast cancer in women is the second most common type of cancer in the United States. It forms in the breast tissue and in advanced cases, spreads to surrounding normal tissue. The National Cancer Institute estimates that 232,670 American women were diagnosed with breast cancer and 40,000 died from the disease in 2014.

Ibrance works by inhibiting molecules, known as cyclin-dependent kinases (CDKs) 4 and 6, involved in promoting the growth of cancer cells. Ibrance is intended for postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole, another FDA-approved product used to treat certain kinds of breast cancer in postmenopausal women.

FDA Approves Ibrance (palbociclib) for Postmenopausal Women with Advanced Breast Cancer

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

In continuation of my updates on palbociclib

Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

 Palbociclib (codenamed PD-0332991, trade name Ibrance)

Pfizer Inc.,  announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

FDA Approves Ibrance (palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer

In continuation of my update on palbociclib

Pfizer  announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for Ibrance (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. The approval is based on data from electronic health records and postmarketing reports of the real-world use of Ibrance in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.

“With this approval, we are now able to offer Ibrance to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We appreciate that our partnership with the FDA has allowed us to take a significant step forward in the use of real-world data to bring medicines to patients who are most in need.”

Ibrance is now approved for adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy. With today’s approval, Ibrance is the first and only CDK 4/6 inhibitor indicated in combination with an aromatase inhibitor for the first-line treatment of men with HR+, HER2- metastatic breast cancer in the U.S.

“Men with breast cancer have limited treatment options, making access to medicines such as Ibrance critically important,” said Bret Miller, founder of the Male Breast Cancer Coalition. “We applaud the use of real-world data, a new approach to drug review, to make Ibrance available to certain men with metastatic breast cancer and help address an unmet need for these patients.”

Real-world data is playing an increasingly important role in expanding the use of already approved innovative medicines.1 Due to the rarity of breast cancer in males, fewer clinical trials are conducted that include men resulting in fewer approved treatment options. In the U.S. in 2019, it is estimated that there will be 2,670 new cases of invasive breast cancer and about 500 deaths from metastatic breast cancer in males.2 The 21st Century Cures Act, enacted in 2016, was created to help accelerate medical product development, allowing new innovations and advances to become available to patients who need them faster and more efficiently.3 This law places additional focus on the use of real-world data to support regulatory decision-making.4

Detailed analysis of the use of Ibrance in men with HR+, HER2- advanced or metastatic breast cancer will be presented at an upcoming medical meeting. Based on limited data from postmarketing reports and electronic health records, the safety profile for men treated with Ibrance is consistent with the safety profile in women treated with Ibrance.5

About Ibrance (palbociclib) 125 mg capsules

Ibrance is an oral inhibitor of CDKs 4 and 6,6 which are key regulators of the cell cycle that trigger cellular progression.7,8 In the U.S., Ibrance is indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

Ibrance currently is approved in more than 90 countries and has been prescribed to more than 200,000 patients globally.

PALOMA3 supports palbociclib use in advanced breast cancer

In continuation of my update on palbociclib... 

Advanced breast cancer patients who have failed prior endocrine treatment may receive a progression-free survival (PFS) benefit if palbociclib is added to fulvestrant, a phase III trial indicates.

The advantage accorded by the small-molecule inhibitor of CDK4 and CDK6 was irrespective of the menopausal status of the women, the team reports in The New England Journal of Medicine.

The research was concurrently presented at the annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA.

The double-blind PALOMA3 trial comprised women with advanced breast cancer positive for oestrogen and/or progesterone hormone receptors but negative for epidermal growth factor receptor 2 who had progressed or relapsed during endocrine therapy.

PALOMA3 supports palbociclib use in advanced breast cancer

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

In continuation of my updates on palbociclib

Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

FDA Approves Revtorpyk (gedatolisib) for the Treatment of HR+/HER2-, PIK3CA Wild-Type Locally Advanced or Metastatic Breast Cancer

Celcuity Inc. (Nasdaq: CELC), a biotechnology company focused on developing and commercializing targeted therapies for multiple solid tumor indications,   announced  the U.S. Food and Drug Administration (“FDA”) approval of  Revtorpyk (gedatolisib) for the treatment of patients with hormone receptor positive (“HR+”), human epidermal growth factor receptor 2 negative (“HER2-”), locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. Revtorpyk is the only inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2 to receive FDA approval.

• Revtorpyk is the first and only FDA-approved therapy that inhibits all class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2
• In the Phase 3 VIKTORIA-1 trial, Revtorpyk combined with palbociclib and fulvestrant and Revtorpyk combined with fulvestrant reduced the risk of disease progression or death by 76% and 67%, respectively, compared to fulvestrant among patients with PIK3CA wild-type advanced or metastatic breast cancer

“The PI3K/AKT/mTOR, or PAM, pathway is one of the most important targets in cancer, but comprehensively inhibiting it has stymied researchers and drug developers for nearly two decades,” said Brian Sullivan, CEO and co-founder of Celcuity. “Revtorpyk addressed this 20-year challenge by becoming the first pan-PI3K, mTORC1/2 inhibitor approved by the FDA. We are thankful for the opportunity to make this important new therapy available to patients with HR+/HER2- locally advanced or metastatic breast cancer.”

HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers.1 Among this breast cancer subtype, approximately 60% have PIK3CA wild-type disease.2

“For patients with HR+/HER2- locally advanced or metastatic breast cancer, there is an urgent need for new treatment options that can meaningfully increase the likelihood of survival without disease progression or death,” said Sara Hurvitz, MD, Senior Vice President, Clinical Research Division, Fred Hutchinson Cancer Center, Smith Family Endowed Chair in Women’s Health and Professor and Head, Division of Hematology and Oncology, University of Washington, School of Medicine and co-principal investigator for the VIKTORIA-1 trial. “With the approval of Revtorpyk, oncologists now have an effective new treatment option for these patients.”

The approval of Revtorpyk is based on positive clinical results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 trial, an open-label, global, randomized clinical trial evaluating the efficacy and safety of Revtorpyk plus fulvestrant, with or without palbociclib, for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 therapy and an aromatase inhibitor. In the VIKTORIA-1 trial, median progression free survival (“PFS”) with the Revtorpyk triplet (Revtorpyk plus palbociclib and fulvestrant) was 9.3 months versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months (HR=0.24; 95% CI: 0.17-0.35; p<0.0001). The objective response rate (“ORR”) of the Revtorpyk triplet was 32% compared to 1% with fulvestrant and the median duration of response (“DOR”) was 17.5 months. For the Revtorpyk doublet (Revtorpyk plus fulvestrant), the median PFS was 7.4 months versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months (HR=0.33; 95% CI: 0.24-0.48; p<0.0001). The ORR of the Revtorpyk doublet was 28% and the median DOR was 12.0 months. The median DOR was not determinable for fulvestrant because there was only one objective response.

“Today’s approval of Revtorpyk addresses a significant unmet need for the thousands of patients affected each year by HR+/HER2-, PIK3CA wild-type locally advanced or metastatic breast cancer whose disease has progressed after endocrine therapy,” said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. “We are deeply grateful to the patients and their caregivers, investigators and clinical study teams, and Celcuity team members who made this advancement possible.”

Celcuity anticipates commercial launch in late Q3 2026. Based on the company’s commitment to ensuring broad, affordable, and unrestricted patient access to Revtorpyk, we have designed a comprehensive patient support program. To make Revtorpyk available to patients prior to commercial launch, those who are eligible will be able to enroll in Celcuity’s expanded access program.

Celcuity plans to submit in Q3 2026 a supplemental New Drug Application (“sNDA”) to the FDA for Revtorpyk for the treatment of HR+/HER2-, PIK3CA mutated, locally advanced or metastatic breast cancer, following at least one line of endocrine therapy based on results from the mutant cohort of the Phase 3 VIKTORIA-1 trial. Results for this study were recently presented in a late-breaking abstract oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Following the sNDA submission, Celcuity intends to submit VIKTORIA-1 data for marketing authorization of gedatolisib to other regulatory authorities around the world.

Revtorpyk is also being studied in the ongoing Phase 3 VIKTORIA-2 clinical trial incorporating two independent studies evaluating two separate patient cohorts with HR+/HER2- locally advanced or metastatic breast cancer who are treatment-naive in the advanced setting.

About Revtorpyk (gedatolisib)

Revtorpyk is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT.3.4.5

Revtorpyk is in development for the first-line treatment of HR+/HER2- locally advanced or metastatic breast cancer and for the second-line treatment of metastatic castration resistant prostate cancer.

Indication Statement

Revtorpyk (gedatolisib) is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.

https://en.wikipedia.org/wiki/Gedatolisib

FDA Approves Revtorpyk (gedatolisib) for the Treatment of HR+/HER2-, PIK3CA Wild-Type Locally Advanced or Metastatic Breast Cancer

FDA Approves Verzenio (abemaciclib) for Certain Advanced or Metastatic Breast Cancers

 

We know that, Abemaciclib is a kinase inhibitor for oraladministration. It is a white to  yellow powder with the empirical formula C₂₇H₃₂F₂N₈

and a molecular weight 506.59.

The chemical name for abemaciclib is 2-Pyrimidinamine,
N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-Abemaciclib  has the above  structure:

The U.S. Food and Drug Administration today approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negativeadvanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzeniois approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It isalso approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer hadspread (metastasized).

"Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alonetreatment to patients who were previously treated with endocrine therapy and chemotherapy," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Combination treatment with CDK4/6 inhibitor improves progression-free survival in HR breast cancer patients

The addition of the CDK4/6 inhibitor ribociclib to letrozole therapy significantly improves progression-free survival in postmenopausal women with hormone receptor-positive advanced breast cancer, researchers reported today at the ESMO 2016 Congress in Copenhagen.

The first interim analysis of data from the randomized, double-blind MONALEESA study showed a 44% improvement in progression-free survival with ribociclib plus letrozole as a first-line treatment combination.

"This was THE definitive study to demonstrate the superiority of the combination of ribociclib and letrozole over letrozole alone," said principle investigator, Professor Gabriel Hortobagyi, from the University of Texas MD Anderson Cancer Center in Houston, Texas, US.

Researchers randomized 668 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, who had not undergone any prior systemic treatment, to ribociclib (600 mg/day, 3 weeks on/1 week off) and letrozole (2.5 mg/day, continuous), or letrozole plus placebo.

                                

ribociclib                                                                                  letrozole

In the ribociclib arm, there was a 44% improvement in the primary objective of progression-free survival compared to the placebo arm (HR: 0.556, p = 0.00000329). Median progression-free survival was 14.7 months in the placebo arm, but was not reached in the ribociclib arm at data cut-off.

"The results of this trial represent a compelling proof of principle, and suggest a paradigm shift in metastatic, HR+ breast cancer. They also suggest that testing combinations of ribociclib with other inhibitors of various signaling pathways might lead to additional progress in the management of several subtypes of breast cancer," Hortobagyi said.

Patients with measurable disease at baseline showed a significantly higher objective response rate to ribociclib plus letrozole compared to letrozole alone (53% vs. 37%; p=0.00028), and improved clinical benefit rate (80% vs. 72% p=0.02).

Serious adverse events occurred in fewer than 5% of patients in both arms but other adverse events were significantly more common in the ribociclib arm. Neutropenia occurred in 59% of patients in the ribociclib arm compared to 1% of the placebo arm; leukopenia occurred in 21% vs 1%; lymphopenia in 7% vs. 1%, and patients in the ribociclib arm had a higher incidence of elevated alanine aminotransferase and elevated aspartate aminotransferase.

The number of deaths in the study was too low to enable a reliable analysis of the impact of ribociclib therapy on overall survival.

Commenting on the findings, Professor Giuseppe Curigliano, Director of the New Drugs and Early Drug Development for Innovative Therapies Division at the European Institute of Oncology, Milan, Italy, said, "I believe the results of this study are significant because now we have a new CDK4/6 inhibitor for patients with estrogen-receptor positive metastatic breast cancer, in addition to palbociclib (already FDA approved) and abemaciclib (under development)."

"The addition of ribociclib to letrozole does increase the rate of toxicity, but overall, if we evaluate the magnitude of clinical benefit, there is definitely a benefit to be gained from adding ribociclib."

Curigliano also suggested that further studies of ribociclib should examine the use of cancer biomarkers to better identify patients who would respond to the combination.