PF-07104091 as a Single Agent and in Combination Therapy

JRCT ID: jRCT2031220134

Registered date:14/06/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Advanced or metastatic breast cancer and other solid tumor
• Date of first enrollment: 11/11/2022
• Target sample size: 320
• Countries of recruitment: United States,Japan,China,Japan,Mexico,Japan
• Study type: Interventional

Intervention(s)

Dose Escalation
*PF-07104091 (orally)
*PF-07104091 (orally) + palbociclib + fulvestrant
*PF-07104091 (orally) + palbociclib + letrozole
Dose Expansion
*PF-07104091 (orally) [SCLC, Ovarian Cancer] (not recruiting in Japan)
*PF-07104091 (orally) + fulvestrant [BC: post CDK4/6i]

Outcome(s)

Primary Outcome

*[Dose Escalation] DLT during first cycle (28 days): Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level
*Treatment emergent adverse events and laboratory abnormalities: Type, incidence, severity, timing, seriousness and relationship will be summarized by dose level (From baseline until end of study treatment or study completion (approximately 2 years))
*Vital signs, heart rate corrected QT interval (From baseline until end of study treatment or study completion (approximately 2 years))
*[Dose Expansion] Preliminary antitumor activity: ORR based on RECIST 1.1 as a single agent and in combination with fulvestrant (From baseline through disease progression or study completion (approximately 2 years))

Secondary Outcome

* Cmax of PF-07104091 after a single and multiple dose
* Tmax of PF-07104091 after a single and multiple dose
* AUClast of PF-07104091
* AUC of PF-07104091 with or without food
* Cmax of PF-07104091 with or without food
* [Dose escalation] Preliminary antitumor activity: ORR based on RECIST 1.1 as a single agent and in combination with palbociclib and fulvestrant or letrozole (From baseline through disease progression or study completion (approximately 2 years))
* Preliminary antitumor activity: Time to event endpoints based on RECIST 1.1 (From baseline through time to event on study or study completion (approximately 2 years))

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

*Participants with HR-positive HER2-negative advanced or metastatic breast cancer (received prior CDK4/6 inhibitor in the advanced or metastatic setting)
*Participants with other advanced or metastatic solid tumor
*Have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated (expansion cohort only)
*Performance Status 0 or 1
*Adequate bone marrow, kidney and liver function
*Resolved acute effects of any prior therapy to baseline severity

Exclude criteria

Exclusion Criteria:
* Participants with known symptomatic brain metastases requiring steroids
* Participants with any other active malignancy within 3 years prior to enrollment
* 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
* 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-CoV2
* Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
* Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, arrhythmias, 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 thrombo embolic disease.
* Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed.
* Hypertension that cannot be controlled by medications
* 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
* 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
* 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 (if applicable).
* Current use or anticipated need for food or drugs that are known strong CYP3A4/5 or UGT1A9 inhibitors or inducers
* Current use or anticipated need for drugs that are known sensitive UGT1A1 substrates with narrow therapeutic
* Serum pregnancy test positive at screening
* Other medical or psychiatric conditio

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT04553133