Locally Advanced or Metastatic Non-small Cell Lung Cancer Clinical Trial
— KAT6Official title:
A Phase 1 Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Anti-tumor Activity of PF-07248144 in Participants With Advanced or Metastatic Solid Tumors.
This is an open-label, multi center study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-07248144 and early signs of clinical efficacy of PF-07248144 as a single agent and in combination with either fulvestrant or letrozole + palbociclib or with PF-07220060 + fulvestrant
Status | Recruiting |
Enrollment | 186 |
Est. completion date | November 8, 2026 |
Est. primary completion date | May 9, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Disease Characteristics - Breast, Prostate, and Lung Cancer - Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available. - Part 1B, Part 1C and Part 1D (Combination Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting. - Part 2A (ER+HER2- breast cancer 2L+, monotherapy) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 line of endocrine therapy. - Part 2B (ER+HER2- breast cancer 2-4L, combination with fulvestrant) Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.. Participants must not have received more than 3 prior lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant. - Part 2D (ER+HER2- breast cancer 2-4L, combination with PF-07220060 (CDK4i) and fulvestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy. - Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant. - Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of ER-positive tumor (=1% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards. - Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4. - Female participants with ER+HER2- advanced or metastatic breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause by treatment with the approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause. - Female participants with ER+HER2- advanced or metastatic breast cancer of nonchildbearing potential must meet at least 1 criteria of achieving postmenopausal status. - Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated. - Eastern Cooperative Oncology Group (ECOG) Performance Status PS 0 or 1 - Female or male patients aged = 18 years (Japan = 20 years) (South Korea = 19 years). - Adequate renal, liver, and bone marrow function. - Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for adverse events (AEs) not constituting a safety risk by investigator judgment. Exclusion Criteria: - Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor). - Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. - Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior to study entry. - Prior irradiation to >25% of the bone marrow. - ECG clinically relevant abnormalities (eg, QTc >470 msec, complete LBBB, second/third degree AV block, ST elevation or EKG changes suggesting myocardial infarction or active myocardia ischemia). - Therapeutic anticoagulation. However, low molecular weight heparin is allowed. Vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor. - Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of PF-07248144. - Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous gastric resection, lap band surgery or other GI conditions and surgeries that may significantly alter the absorption of PF-07248144 tablets. Gastroesophageal reflux disease under treatment is allowed. - Pregnant or breastfeeding female participants. |
Country | Name | City | State |
---|---|---|---|
Australia | Cancer Research South Australia | Adelaide | South Australia |
Australia | Chris O'Brien Lifehouse | Camperdown | New South Wales |
Australia | Peter MacCallum Cancer Centre | Melbourne | Victoria |
Australia | Royal Melbourne Hospital | Parkville | Victoria |
Australia | Western Health-Sunshine & Footscray Hospitals | St Albans | Victoria |
Australia | St. John of God Subiaco Hospital | Subiaco | Western Australia |
China | Beijing Cancer hospital | Beijing | Beijing |
China | Jilin Cancer Hospital | Changchun | Jilin |
China | SUN Yat-Sen University Cancer Center | Guangzhou | Guangdong |
China | Hubei Cancer Hospital | Wuhan | Hubei |
China | The First Affiliated Hospital of Xi'an Jiaotong University | Xi'an | Shaanxi |
Japan | National Cancer Center Hospital | Chuo-ku | Tokyo |
Japan | National Cancer Center Hospital East | Kashiwa | Chiba |
Japan | Aichi Cancer Center Hospital | Nagoya | Aichi |
Japan | Kanagawa cancer center | Yokohama | Kanagawa |
Korea, Republic of | Kyungpook National University Chilgok Hospital | Daegu | Taegu-kwangyokshi |
Korea, Republic of | Seoul National University Bundang Hospital | Seongnam | Ky?nggi-do |
Korea, Republic of | Asan Medical Center | Seoul | |
Korea, Republic of | Samsung Medical Center | Seoul | Seoul-teukbyeolsi [seoul] |
Korea, Republic of | Seoul National University Hospital | Seoul | Seoul-teukbyeolsi [seoul] |
Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | Seoul-teukbyeolsi [seoul] |
United States | St. Elizabeth Healthcare | Edgewood | Kentucky |
United States | Michigan Health Professionals | Farmington Hills | Michigan |
United States | Revive Research Institute | Farmington Hills | Michigan |
United States | Holy Cross Hospital | Fort Lauderdale | Florida |
United States | Holy Cross Hospital | Fort Lauderdale | Florida |
United States | Tennessee Oncology PLLC | Franklin | Tennessee |
United States | The University of Texas M. D. Anderson Cancer Center | Houston | Texas |
United States | U.T. MD Anderson Cancer Center | Houston | Texas |
United States | Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute | Los Angeles | California |
United States | Cedars-Sinai Medical Center; SOCCI Pharmacy | Los Angeles | California |
United States | James Graham Brown Cancer Center | Louisville | Kentucky |
United States | University Medical Center, lnc.:DBA University of Louisville Hospital | Louisville | Kentucky |
United States | Sarah Cannon Research Institute | Nashville | Tennessee |
United States | Tennessee Oncology PLLC | Nashville | Tennessee |
United States | The Sarah Cannon Research Institute / Tennessee Oncology, PLLC | Nashville | Tennessee |
United States | Smilow Cancer Hospital at Yale - New Haven | New Haven | Connecticut |
United States | Smilow Cancer Hospital Phase 1 Unit | New Haven | Connecticut |
United States | Yale New Haven Hospital | New Haven | Connecticut |
United States | Yale University - Yale Cancer Center | New Haven | Connecticut |
United States | Yale-New Haven Hospital | New Haven | Connecticut |
United States | Yale-New Haven Hospital- Yale Cancer Center | New Haven | Connecticut |
United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Bodine Center for Radiation Therapy | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Clinical Research Unit | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Gibbon Building | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Investigational Drug Service | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Main Office Building | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Sidney Kimmel Cancer Center | Philadelphia | Pennsylvania |
United States | Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization | Philadelphia | Pennsylvania |
United States | TJU Research PK/PD Lab | Philadelphia | Pennsylvania |
United States | NEXT Oncology | San Antonio | Texas |
United States | UCSF Medical Center at Mission Bay | San Francisco | California |
United States | HonorHealth | Scottsdale | Arizona |
United States | Swedish Cancer Institute | Seattle | Washington |
United States | Swedish Medical Center | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Pfizer |
United States, Australia, China, Japan, Korea, Republic of,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of participants with dose-limiting toxicities in the Dose Escalation Arms. | Dose-limiting toxicities (DLTs) | Up to 29 days | |
Primary | Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. | Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. | Up to 24 months | |
Primary | Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Up to 24 months | |
Primary | Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms | Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. | Up to 24 months | |
Primary | Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Up to 24 months | |
Secondary | Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Multiple Dose: Steady state AUC during a dosage interval (t) (AUCt,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms. | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms. | Pharmacokinetic (PK) assessments for PF-07248144 and PF-07220060 (Part 1D) | Up to 24 months | |
Secondary | Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm. | Pharmacokinetic (PK) assessment for palbociclib exposure. | Up to 24 months | |
Secondary | Best Overall Response (BOR) in participants in the Dose Expansion Arms | Up to 24 months | ||
Secondary | Duration of Response (DOR) in participants enrolled in the Dose Expansion Arms | Up to 24 months | ||
Secondary | Peak concentrations of PF-07248144 and PF-07220060 (Part 2D) for selected cycles in the Dose Expansion Arms | Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D) | Up to 24 months | |
Secondary | Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms | Pharmacokinetic (PK) assessment for PF-07248144 and PF-07220060 (Part 2D) | Up to 24 months | |
Secondary | Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF-07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) | |
Secondary | Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF-07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) | |
Secondary | AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF 07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) | |
Secondary | Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm. | Evaluate urine pharmacokinetic (PK) of PF-07248144. | Up to 24 months | |
Secondary | Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm | Evaluate urine pharmacokinetic (PK) of PF-07248144. | Up to 24 months | |
Secondary | Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms | Up to 24 months | ||
Secondary | Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms | Up to 24 months | ||
Secondary | Overall survival (OS) observed in participants enrolled in Dose Expansion Arms | Up to 24 months | ||
Secondary | Best Overall Response (BOR) observed in participants in the dose expansion arms | Up to 24 months | ||
Secondary | Duration of Response (DOR) observed in participants in the dose expansion arms | up to 24 months | ||
Secondary | Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms | up to 24 months |
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