PF-07104091 as a Single Agent and in Combination Therapy

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04553133

Collaborator

(none)

240

Enrollment

Locations

Arms

85.7

Anticipated Duration (Months)

10.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the safety and tolerability of increasing doses of PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended Phase 2 dose (RP2D) for PF-07104091 as a single agent in participants with small cell lung, non small cell lung, and ovarian and breast cancers.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer Ovarian Cancer Breast Cancer Triple-Negative Breast Cancer Non Small Cell Lung Cancer	Drug: PF-07104091 monotherapy dose escalation Drug: PF-07104091 + palbociclib + fulvestrant Drug: PF-07104091 + palbociclib + letrozole Drug: PF-07104091 monotherapy dose expansion (ovarian) Drug: PF-07104091 monotherapy dose expansion (SCLC) Drug: PF-07104091 monotherapy dose expansion (TNBC) Drug: PF-07104091 + palbociclib + fulvestrant (post CDK4/6) Drug: PF-07104091 + palbociclib + fulvestrant (CDK4/6 naive) Drug: PF-07104091 + palbociclib + letrozole (CDK4/6 naive)	Phase 2

Detailed Description

Study C4161001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-07104091 in adult patients with advanced or metastatic small cell lung cancer (SCLC), advanced platinum resistant epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer, locally recurrent/advanced or metastatic triple negative breast cancer (TNBC), HR-positive HER2-negative advanced or mBC, advanced or metastatic non-small cell lung cancer (NSCLC). This two part study will assess the safety and tolerability of increasing dose levels of PF-07104091 in Part 1, and establish the recommended Phase 2 dose (RP2D) in Part 2.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 16, 2020

Anticipated Primary Completion Date :

Nov 8, 2026

Anticipated Study Completion Date :

Nov 8, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-07104091 CDK2 monotherapy dose escalation	Drug: PF-07104091 monotherapy dose escalation PF-07104091 will be administered orally
Experimental: PF-07104091 + palbociclib + fulvestrant CDK2 + palbociclib + fulvestrant	Drug: PF-07104091 + palbociclib + fulvestrant PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
Experimental: PF-07104091 + palbociclib + letrozole CDK2 + palbociclib + letrozole	Drug: PF-07104091 + palbociclib + letrozole PF-07104091 will be administered orally in combination with palbociclib and letrozole
Experimental: PF-07104091 monotherapy dose expansion (SCLC) PF-07104091 monotherapy dose expansion (SCLC)	Drug: PF-07104091 monotherapy dose expansion (SCLC) PF-07104091 will be administered orally
Experimental: PF-07104091 monotherapy dose expansion (ovarian) PF-07104091 monotherapy dose expansion (ovarian)	Drug: PF-07104091 monotherapy dose expansion (ovarian) PF-07104091 will be administered orally
Experimental: PF-07104091 monotherapy dose expansion (TNBC) PF-07104091 monotherapy dose expansion (TNBC)	Drug: PF-07104091 monotherapy dose expansion (TNBC) PF-07104091 will be administered orally
Experimental: PF-07104091 + palbociclib + fulvestrant (post CDK4/6) PF-07104091 + palbociclib + fulvestrant (post CDK4/6)	Drug: PF-07104091 + palbociclib + fulvestrant (post CDK4/6) PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
Experimental: PF-07104091 + palbociclib + fulvestrant (CDK4/6 naive) PF-07104091 + palbociclib + fulvestrant (CDK4/6 naive)	Drug: PF-07104091 + palbociclib + fulvestrant (CDK4/6 naive) PF-07104091 will be administered orally in combination with palbociclib and fulvestrant
Experimental: PF-07104091 + palbociclib + letrozole (CDK4/6 naive) PF-07104091 + palbociclib + letrozole (CDK4/6 naive)	Drug: PF-07104091 + palbociclib + letrozole (CDK4/6 naive) PF-07104091 will be administered orally in combination with palbociclib and fulvestrant

Outcome Measures

Primary Outcome Measures

Dose Escalation: Number of participants with Dose-limiting toxicities (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
To evaluate incidence of treatment emergent adverse events and laboratory abnormalities [From baseline until end of study treatment or study completion (approximately 2 years)]
Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities will be summarized by dose level
Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline [From baseline until end of study treatment or study completion (approximately 2 years)]
Identify pulse rate readings that are outside the normal range. The number and percentage of participants who experienced significant pulse rate change from baseline will be summarized by dose level
Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline [From baseline until end of study treatment or study completion (approximately 2 years)]
Identify systolic and diastolic readings that are outside the normal range. The number and percentage of participants who experienced significant blood pressure change from baseline will be summarized by dose level
To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline [From baseline until end of study treatment or study completion (approximately 2 years)]
Determine the effect of the drug on QT prolongation. The number and percentage of participants who experienced QT interval prolongation will be summarized by dose level
To evaluate the preliminary antitumor activity of PF-07104091 as a single agen and in combination with palbociclib and in combination with letrozole by objective response rate (ORR) in dose expansion [From baseline through disease progression or study completion (approximately 2 years)]
Percentage of participants with a best overall response of complete response (CR) or partial response (PR) using RECIST 1.1

Secondary Outcome Measures

Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose [Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)]
Peak concentration of PF-07104091 during selected cycles
Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose [Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)]
Time to peak concentration of PF-07104091 during selected cycles
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07104091 [Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)]
AUC of PF-07104091 will be calculated at selected cycles
Area under the curve of PF-07104091 with or without food [From baseline through time to event on study or study completion (approximately 2 years)]
AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
Maximum plasma concentration of PF-07104091 with or without food [From baseline through time to event on study or study completion (approximately 2 years)]
Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
To document any preliminary evidence of antitumor activity of PF-07104091 as a single agen and in combination with palbociclib and in combination with letrozole by objective response rate (ORR) in dose escalation [From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)]
Percentage of participants with a best overall response of CR or PR using RECIST 1.1
To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints [From baseline through time to event on study or study completion (approximately 2 years)]
Time from first assessment of event endpoint to last assessment of using RECIST 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with HR-positive HER2-negative advanced or metastatic breast cancer (received at least two prior lines in the advanced or metastatic setting including one prior line of combined CDK4/6 inhibitor and endocrine therapy and no more than two prior lines of cytotoxic chemotherapy)
Participants with locally recurrent/advanced or metastatic TNBC who have received up to 2 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
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).
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
Performance Status 0 or 1
Adequate bone marrow, hematological, kidney and liver function
Resolved acute effects of any prior therapy to baseline severity

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 condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Clive	Iowa	United States	50325
2	Des Moines Oncology Research Association	Des Moines	Iowa	United States	50309
3	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Des Moines	Iowa	United States	50309
4	Medical Oncology & Hematology Associates DBA Mission Cancer and Blood	Des Moines	Iowa	United States	50314
5	Norton Cancer Institute Downtown	Louisville	Kentucky	United States	40202
6	Norton Cancer Institute Pharmacy, Downtown Pharmacy	Louisville	Kentucky	United States	40202
7	Norton Cancer Institute, Downtown	Louisville	Kentucky	United States	40202
8	Norton Hospital	Louisville	Kentucky	United States	40202
9	Norton Diagnostic Center - Dupont	Louisville	Kentucky	United States	40207
10	Brownsboro Diagnostic Center	Louisville	Kentucky	United States	40241
11	Norton Diagnostic Center - Fern Creek	Louisville	Kentucky	United States	40291
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
14	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
15	START Midwest	Grand Rapids	Michigan	United States	49546
16	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
17	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
18	MSK Rockefeller Outpatient Pavilion	New York	New York	United States	10022
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
20	Tennessee Oncology PLLC	Franklin	Tennessee	United States	37067
21	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
22	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
23	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030