PF-07220060 for Solid Cancers (CDK4i Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Pfizer
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new drug, PF-07220060, in patients with metastatic breast cancer. It aims to find the best dose and see if the drug helps stop cancer growth when used alone or with other treatments.
Is the drug PF-07220060 a promising treatment for solid cancers?The information provided does not mention PF-07220060 or Atirmociclib, so we cannot determine if it is a promising treatment for solid cancers based on this data.124510
What data supports the idea that PF-07220060 for Solid Cancers is an effective drug?The available research does not provide specific data on the effectiveness of PF-07220060 for Solid Cancers. The studies mentioned focus on other treatments and conditions, such as non-small cell lung cancer and BRAF V600E-mutant cancers, but do not include information on PF-07220060. Therefore, there is no data here to support the effectiveness of PF-07220060 for Solid Cancers.1112131415
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you must not have had any anti-cancer treatment within 2 weeks before starting the study intervention. It's best to discuss your specific medications with the trial team.
What safety data is available for PF-07220060 (Atirmociclib)?The provided research does not contain specific safety data for PF-07220060 or Atirmociclib. It discusses safety profiles of other CDK4/6 inhibitors like palbociclib and ribociclib, and other unrelated drugs like vemurafenib and sorafenib. For PF-07220060, specific clinical trial data or studies would be needed to assess its safety profile.36789
Eligibility Criteria
This trial is for adults with advanced solid tumors, including specific breast and prostate cancers, who have not responded to existing therapies. Participants must have a certain level of physical fitness (ECOG PS 0 or 1) and adequate organ function. They should not have received cancer treatment within the last 2 weeks or be pregnant/breastfeeding.Inclusion Criteria
My breast cancer is HR+ and HER2- and does not respond to hormone therapy.
My breast cancer is HR-positive and HER2-negative.
I have a measurable cancer lesion on my skin or bone.
My condition hasn't improved with current treatments.
I am fully active or restricted in physically strenuous activity but can do light work.
My cancer is NSCLC, prostate, CRC, liposarcoma, or has CDK4/CCND1 amplification.
My prostate cancer has spread and is not responding to hormone therapy.
Exclusion Criteria
I do not have active brain metastases or related conditions.
I haven't had any cancer except for certain skin cancers or localized cancer that hasn't spread in the last 3 years.
I have previously been treated with medications targeting cancer cell growth.
I have not had major surgery or radiation in the last 4 weeks.
I have an active stomach or bowel disease, or I've had surgery on my stomach.
Treatment Details
The study tests PF-07220060's safety and effects both alone and with endocrine therapy in multiple doses. It includes patients with various cancers such as lung adenocarcinoma, colorectal cancer, liposarcoma, prostate cancer, and breast cancer.
17Treatment groups
Experimental Treatment
Group I: 2E Combination Dose ExpansionExperimental Treatment2 Interventions
PF-07220060 Monotherapy OR PF-07220060 plus fulvestrant combination therapy
Group II: 2D Combination Dose ExpansionExperimental Treatment2 Interventions
PF-07220060 with enzalutamide Combination Expansion
Group III: 2C Combination Dose ExpansionExperimental Treatment2 Interventions
PF-07220060 with fulvestrant Combination Expansion
Group IV: 2B Combination Dose ExpansionExperimental Treatment2 Interventions
PF-07220060 with Letrozole Combination Expansion
Group V: 2A Combination Dose ExpansionExperimental Treatment2 Interventions
PF-07220060 with fulvestrant combination dose expansion
Group VI: 1F Combination Dose FindingExperimental Treatment2 Interventions
PF-07220060 with Enzalutamide Escalation
Group VII: 1E DDI CohortExperimental Treatment2 Interventions
PF-07220060 DDI with Midazolam
Group VIII: 1D Monotherapy Food EffectExperimental Treatment1 Intervention
PF-07220060 Monotherapy Food Effect
Group IX: 1C Combination Dose Finding Arm 2Experimental Treatment2 Interventions
PF-07220060 with Fulvestrant Combination Escalation
Group X: 1C Combination Dose Finding Arm 1Experimental Treatment2 Interventions
PF-07220060 with Fulvestrant Combination Escalation
Group XI: 1B Combination Dose Finding Arm 2Experimental Treatment2 Interventions
PF-07220060 with Letrozole Combination Escalation
Group XII: 1B Combination Dose Finding Arm 1Experimental Treatment2 Interventions
PF-07220060 with Letrozole combination Escalation
Group XIII: 1A Monotherapy Escalation Arm 5Experimental Treatment1 Intervention
PF-07220060 Monotherapy Escalation
Group XIV: 1A Monotherapy Escalation Arm 4Experimental Treatment1 Intervention
PF-07220060 Monotherapy Escalation
Group XV: 1A Monotherapy Escalation Arm 3Experimental Treatment1 Intervention
PF-07220060 Monotherapy Escalation
Group XVI: 1A Monotherapy Escalation Arm 2Experimental Treatment1 Intervention
PF-07220060 Monotherapy Escalation
Group XVII: 1A Monotherapy Escalation Arm 1Experimental Treatment1 Intervention
PF-07220060 Monotherapy Escalation
Find a clinic near you
Research locations nearbySelect from list below to view details:
Sarah Cannon Research Institute - PharmacyNashville, TN
Tennessee Oncology, PLLCFranklin, TN
Ellison InstituteLos Angeles, CA
Yale-New Haven Hospital-Yale Cancer CenterNew Haven, CT
More Trial Locations
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Who is running the clinical trial?
PfizerLead Sponsor
References
Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. [2022]Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.
Sorafenib. [2018]Sorafenib (BAY 43-9006, Nexavar) is a novel oral kinase inhibitor that targets multiple tyrosine kinases in vivo and in vitro. Main targets are receptor tyrosine kinase pathways frequently deregulated in cancer such as the raf-ras pathway, vascular endothelial growth factor (VEGF) pathway, and FMS-like tyrosine kinase 3 (FLT3). Sorafenib was approved by the FDA in fast track for advanced renal cell cancer and hepatocellular cancer and shows good clinical activity in thyroid cancer. Multiple clinical trials are undertaken to further investigate the role of sorafenib alone or in combination for the treatment of various tumor entities.
Sorafenib in melanoma. [2020]Sorafenib is an orally available multi-kinase inhibitor that inhibits tumor proliferation by targeting multiple kinases including the vascular endothelial growth factor receptors VEGFR1, VEGFR2, VEGFR3 and the platelet-derived growth factor receptor PDGFR, and it targets tumor progression by inhibiting FLT3, C-Kit and BRAF. Since BRAF mutations are frequent in melanoma, sorafenib was investigated in various Phase I, II and III clinical trials. The drug is well tolerated with mild to moderate adverse effects, which are mostly limited to cutaneous toxicity, diarrhea and fatigue.
Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials. [2023]Angiogenesis is an integral process in carcinogenesis, and molecular inhibitors of angiogenic factors are currently being tested as treatments for cancer. Sunitinib is an oral multitargeted tyrosine-kinase inhibitor that blocks activation through the stem cell-factor receptor (Kit) and platelet-derived growth-factor receptor. Sunitinib has shown potent antitumor activity against several solid tumors, including renal cell carcinoma, gastrointestinal stromal tumors, and neuroendocrine tumors in several Phase II/III trials. Recently, sunitinib has been used to treat other solid cancers, such as lung cancer, pancreatic cancer, chondrosarcoma, esophageal cancer, bladder cancer, glioma, and aggressive fibromatosis, and also showed potential efficacy in progression-free survival and overall survival. In this review, we examine the efficacy of sunitinib as a molecular-targeted therapy in patients with different types of solid cancers.
[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.
Sorafenib-associated facial acneiform eruption. [2020]Sorafenib is an oral multikinase inhibitor that targets tumor cell angiogenesis and proliferation. Drug-associated cutaneous adverse events, such as alopecia and hand-foot skin reaction, occur frequently. Sorafenib-related side effects affecting hair, nails, and skin are summarized and the characteristics of sorafenib-treated patients who developed acneiform facial lesions are reviewed to present the clinical features of these individuals.
Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis. [2022]Label="BACKGROUND">The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAFV600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety.
Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib. [2022]Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib and ribociclib are associated with distinct adverse effects (AEs) compared to other targeted therapies. This meta-analysis of clinical trials summarizes these agents' toxicity profile.
Updates on managing advanced breast cancer with palbociclib combination therapy. [2023]The objective of this study was to review the pharmacology, efficacy, and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of advanced breast cancer (ABC).
Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies. [2023]Label="BACKGROUND">BRAF inhibitors are effective against selected BRAFV600 -mutated tumors. Preclinical data suggest that BRAF inhibition in conjunction with chemotherapy has increased therapeutic activity.
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Non-Small Cell Lung Cancer Responds to Osimertinib plus Savolitinib. [2022]In a phase Ib trial, osimertinib plus savolitinib showed efficacy in non-small cell lung cancer.
A Novel MYH9-RET Fusion Occurrence and EGFR T790M Loss as an Acquired Resistance Mechanism to Osimertinib in a Patient with Lung Adenocarcinoma: A Case Report. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Osimertinib is a novel and irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeting EGFR sensitive mutations and EGFR exon20 p.T790M mutation, which demonstrated superior progression-free survival (PFS) and overall survival (OS).
BRAF v600E-mutant cancers treated with vemurafenib alone or in combination with everolimus, sorafenib, or crizotinib or with paclitaxel and carboplatin (VEM-PLUS) study. [2023]Combined BRAF + MEK inhibition is FDA approved for BRAF V600E-mutant solid tumors except for colorectal cancer. However, beyond MAPK mediated resistance several other mechanisms of resistance such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway exist among other complex pathways. In the VEM-PLUS study, we performed a pooled analysis of four phase one studies evaluating the safety and efficacy of vemurafenib monotherapy and vemurafenib combined with targeted therapies (sorafenib, crizotinib, or everolimus) or carboplatin plus paclitaxel in advanced solid tumors harboring BRAF V600 mutations. When vemurafenib monotherapy was compared with the combination regimens, no significant differences in OS or PFS durations were noted, except for inferior OS in the vemurafenib and paclitaxel and carboplatin trial (P = 0.011; HR, 2.4; 95% CI, 1.22-4.7) and in crossover patients (P = 0.0025; HR, 2.089; 95% CI, 1.2-3.4). Patients naïve to prior BRAF inhibitors had statistically significantly improved OS at 12.6 months compared to 10.4 months in the BRAF therapy refractory group (P = 0.024; HR, 1.69; 95% CI 1.07-2.68). The median PFS was statistically significant between both groups, with 7 months in the BRAF therapy naïve group compared to 4.7 months in the BRAF therapy refractory group (P = 0.016; HR, 1.80; 95% CI 1.11-2.91). The confirmed ORR in the vemurafenib monotherapy trial (28%) was higher than that in the combination trials. Our findings suggest that, compared with vemurafenib monotherapy, combinations of vemurafenib with cytotoxic chemotherapy or with RAF- or mTOR-targeting agents do not significantly extend the OS or PFS of patients who have solid tumors with BRAF V600E mutations. Gaining a better understanding of the molecular mechanisms of BRAF inhibitor resistance, balancing toxicity and efficacy with novel trial designs are warranted.
FOLFOXIRI Plus Cetuximab or Bevacizumab as First-Line Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer: The Randomized Phase II FIRE-4.5 (AIO KRK0116) Study. [2023]Label="PURPOSE"> BRAFV600E mutation is associated with a poor outcome in metastatic colorectal cancer (mCRC). This clinical trial investigated the efficacy of triplet chemotherapy (fluorouracil, folinic acid, oxaliplatin, and irinotecan) combined with either cetuximab or bevacizumab in patients with previously untreated BRAFV600E-mutant mCRC.