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PHASE 1/2A DOSE ESCALATION, FINDING AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07104091 AS A SINGLE AGENT AND IN COMBINATION THERAPY
EU CTIS ID: 2024-515492-34-00
What this study is testing
PART 1A:Safety and tolerability of PF-07104091 in patients with HR+ HER2- advanced or mBC patients, recurrent/advanced or mTNBC or advanced platinum resistant epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer or advanced small cell and non small cell lung cancer to estimate the MTD and select the RDE for PF-07104091 as a single agent. Parts 1B and 1C: Safety and tolerability of PF-07104091 at the single agent RDE in combination with endocrine therapy (Fulvestrant or Letrozole) or endocrine therapy and palbociclib in HR+ HER2- advanced or mBC in order to establish the RDE for PF-07104091 in combination. Part 2: Evaluate antitumor activity and confirm the safety and tolerability of PF-07104091 alone in advanced or metastatic SCLC, advanced platinum resistant epithelial ovarian cancer/fallopian tube/primary peritoneal cancer, TNBC and advanced or metastatic NSCLC or in combination with fulvestrant (doublet) in patients with HR+ HER2- advanced or mBC.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Females and/or male participants age ≥18 years.
- 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.
- 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).
- 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.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- 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.
You likely can't join if
- Participants with known symptomatic brain metastases requiring steroids.
- 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).
- Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed. Anticoagulation with subcutaneous heparin is allowed.
- Hypertension that cannot be controlled by medications (eg, >150/90 mmHg) despite optimal medical therapy.
- Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.
- Known or suspected hypersensitivity to active ingredient/excipients in PF-07104091.
See the full eligibility criteria
Who can join
- Females and/or male participants age ≥18 years.
- 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.
- 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).
- 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.
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- 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.
- 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.
- 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).
- Part 2A: • Participants with cytological diagnosis of advanced / metastatic SCLC
- Part 2B: • Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven)
- Part 2C: • Participants with HR-postive HER2-negative advanced or metastatic breast cancer after prior ET-CDK4/6 inhibitor therapy (histologically or cytologically proven).
- 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).
- ECOG PS 0 or 1.
- 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.
What rules you out
- Participants with known symptomatic brain metastases requiring steroids.
- 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).
- Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed. Anticoagulation with subcutaneous heparin is allowed.
- Hypertension that cannot be controlled by medications (eg, >150/90 mmHg) despite optimal medical therapy.
- Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.
- Known or suspected hypersensitivity to active ingredient/excipients in PF-07104091.
- Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
- 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).
- 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).
- Previous high dose chemotherapy requiring stem cell rescue.
- Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin.
- 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.
- Known or suspected hypersensitivity to active ingredient/excipients of PF-07104091, palbociclib (or equivalent agent to induce chemical menopause).
- 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.
- 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.
- 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).
- Serum pregnancy test (for females of childbearing potential) positive at screening. Breastfeeding female patients (including patients who intend to interrupt breastfeeding).
- 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.
- 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.
- Major surgery within 3 weeks prior to study entry.
- Radiation therapy within 3 weeks prior to study entry.
- 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.
- Prior irradiation to >25% of the bone marrow.
- Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, and known HIV or AIDS related illness.
- COVID-19/SARS-CoV-2: This protocol excludes participants with active infections, as noted above.
- Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
The study team makes the final eligibility decision.
Where it's taking place
- China
- United States
- Argentina
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include China; United States; Argentina. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.