[(1R,3S)-3-[3-[[5-(METHOXYMETHYL)-2-METHYLPYRAZOLE-3-CARBONYL]AMINO]-1H-PYRAZOL-5-YL]CYCLOPENTYL]N-PROPAN-2-YLCARBAMATE MONOHYDRATE for Advanced breast cancer | Ovarian cancer | Small cell lung cancer | Non-small cell lung cancer | Triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"- Females and/or male participants age ≥18 years.\n- Part 1: • Participants with HR-positive HER2-negative advanced or metastatic breast cancer (third line plus setting) (histologically or cytologically proven). • Participants with locally recurrent/advanced or metastatic TNBC who have received up to 3 prior lines of chemotherapy in the advanced or metastatic setting. • Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven) who have received at least 1 systemic anti-cancer therapy containing a platinum analog.\n- Part 1A only: • Participants with cytological diagnosis of advanced/metastatic SCLC. • Participants with or cytological diagnosis of advanced/metastatic NSCLC. • Participants with HR-positive HER2-negative advanced or metastatic breast cancer (second line plus setting) (histologically or cytologically proven).\n- Part 2A: • Participants with cytological diagnosis of advanced / metastatic SCLC\n- Part 2B: • Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven)\n- Part 2C: • Participants with HR-postive HER2-negative advanced or metastatic breast cancer after prior ET-CDK4/6 inhibitor therapy (histologically or cytologically proven).\n- Participants entering the study in the expansion cohort have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated).\n- ECOG PS 0 or 1.\n- Adequate Bone Marrow Function, including: a. ANC ≥1,500/mm3 or ≥1.5 x 109/L; b. Platelets ≥100,000/mm3 or ≥100 x 109/L; c. Hemoglobin ≥9 g/dL.\n- Adequate Renal Function, including: a. Estimated creatinine clearance ≥50 acceptable as calculated using the method standard for the institution. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately.\n- Adequate Liver Function, including: a. Total serum bilirubin ≤1.5 x ULN unless the participant has documented Gilbert syndrome; b. AST and ALT ≤2.5 x ULN; ≤5.0 x ULN if there is liver involvement by the tumor; c. Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).\n- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk by investigator judgment.\n- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.\n- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol."}

Exclusion criteria

• {"criterion_text":"- Participants with known symptomatic brain metastases requiring steroids.\n- Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), serious conduction system abnormalities, unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thromboembolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE ≥ Grade 2, atrial fibrillation of any grade (≥ Grade 2 in the case of asymptomatic lone atrial fibrillation).\n- Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed. Anticoagulation with subcutaneous heparin is allowed.\n- Hypertension that cannot be controlled by medications (eg, >150/90 mmHg) despite optimal medical therapy.\n- Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.\n- Known or suspected hypersensitivity to active ingredient/excipients in PF-07104091.\n- Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.\n- Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).\n- Participants with an indwelling catheter that has an external component such as those used for drainage of effusion(s) or central venous catheter that is externally exposed (eg, peripherally inserted central catheter (PICC) line).\n- Previous high dose chemotherapy requiring stem cell rescue.\n- Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin.\n- 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.\n- Known or suspected hypersensitivity to active ingredient/excipients of PF-07104091, palbociclib (or equivalent agent to induce chemical menopause).\n- Current use or anticipated need for food or drugs that are known strong CYP3A4/5 or UGT1A9 inhibitors, including their administration within 5 half-lives of the CYP3A4/5 or UGT1A9 inhibitor prior to first dose of investigational product.\n- Current use or anticipated need for drugs that are known strong CYP3A4/5 or UGT1A9 inducers, including their administration within 5 half-lives of the CYP3A4/5 or UGT1A9 inducer prior to the first dose of investigational product.\n- Current use or anticipated need for drugs that are known sensitive UGT1A1 substrates with narrow therapeutic index (eg SN-38 [active metabolite of irinotecan], irinotecan, belinostat).\n- Serum pregnancy test (for females of childbearing potential) positive at screening. Breastfeeding female patients (including patients who intend to interrupt breastfeeding).\n- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.\n- Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.\n- Major surgery within 3 weeks prior to study entry.\n- Radiation therapy within 3 weeks prior to study entry.\n- Systemic anti-cancer therapy within 4 weeks prior to study entry (6 weeks for mitomycin C or nitrosoureas) or 5 half-lives (whichever is shorter) of the agent(s) prior to receive the study intervention treatment is required.\n- Prior irradiation to >25% of the bone marrow.\n- Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, and known HIV or AIDS related illness.\n- COVID-19/SARS-CoV-2: This protocol excludes participants with active infections, as noted above.\n- Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results."}

Primary endpoints

• {"endpoint_text":"- Part 1A, Part 1B and Part 1C: •First cycle DLTs. •AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy. •Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. •Vital sign abnormalities. •Heart rate corrected QT interval (eg, QTcF).","definition_or_measurement_approach":"First cycle dose-limiting toxicities (DLTs); adverse events characterized by type/frequency/severity/timing/seriousness/relationship to therapy; laboratory abnormalities graded by NCI CTCAE v5.0; vital signs and QTcF (heart rate corrected QT interval)."}
• {"endpoint_text":"- Part 2 •Preliminary antitumor activity measure for efficacy includes ORR, as assessed using RECIST 1.1. •Safety and tolerability: •Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study therapy.•“Please refer protocol section 3 for more details.”","definition_or_measurement_approach":"Objective response rate (ORR) assessed by RECIST version 1.1; safety/tolerability assessed via adverse events graded by NCI CTCAE v5.0 and other safety measures."}

Secondary endpoints

• {"endpoint_text":"- PK parameters of PF-07104091: •Single Dose Cmax, Tmax, AUClast, and as data permit, AUCinf, CL/F, Vz/F, and t1/2. •Multiple Dose (assuming steady state is achieved) Cmax,ss, Tmax,ss, AUCτ,ss, Cmin,ss, CL/F,ss, and as data permit, V/F, ss, t1/2, and Rac (AUCτ,ss/AUCτ,sd).","definition_or_measurement_approach":"Standard PK parameters (Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, t1/2 for single dose; steady-state PK for multiple doses including Cmax,ss, AUCτ,ss, Cmin,ss, CL/F,ss, Rac)."}
• {"endpoint_text":"- ORR, as assessed using RECIST version 1.1.","definition_or_measurement_approach":"Objective response rate measured per RECIST 1.1."}
• {"endpoint_text":"- Time to event endpoints: eg, DoR, PFS, TTP, CBR.","definition_or_measurement_approach":"Time-to-event measures such as Duration of Response (DoR), Progression-Free Survival (PFS), Time To Progression (TTP), Clinical Benefit Rate (CBR) as defined in protocol."}
• {"endpoint_text":"- Time to event endpoints: eg, DoR, PFS, CBR, overall survival OS and TTP.","definition_or_measurement_approach":"Time-to-event endpoints including DoR, PFS, CBR, overall survival (OS), and TTP."}
• {"endpoint_text":"- •PK parameters of PF-07104091. •Single dose: Cmax, Tmax and AUClast. •Multiple dose (assuming steady state is achieved): Cmax,ss, Tmax,ss, AUClast, Cmin,ss, and Rac.","definition_or_measurement_approach":"Pharmacokinetic parameters for single and multiple dosing (Cmax, Tmax, AUClast, Cmin,ss, Rac)."}
• {"endpoint_text":"- PK parameters of PF-07104091 given with and without food.","definition_or_measurement_approach":"Comparison of PK parameters when PF-07104091 is administered with and without food (food-effect study assessments)."}
• {"endpoint_text":"- Changes in cell cycle biomarkers (eg, phosphor Rb, Ki 67) in paired pre- and on treatment tumor biopsies.","definition_or_measurement_approach":"Evaluation of cell cycle biomarker changes (phospho-Rb, Ki-67) in paired tumor biopsies pre- and on-treatment."}

Bulgaria

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

494

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Virtual Central Lab, Kit build with kit distribution, project management and sample logistics for Ex; Primary/ surrogate endpoint test

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Virtual Central Lab, Kit build with kit distribution, project management and sample logistics for Ex; Primary/ surrogate endpoint test","organisation_type":"Pharmaceutical company"}