Neoplasms

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All Conditions

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Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

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Neoplasms, Adipose Tissue

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All Drugs and Chemicals

Adjuvants, Anesthesia

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Enzyme Inhibitors

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Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

PF-07220060 with Letrozole combination Escalation

PF-07220060 with Letrozole Combination Escalation

PF-07220060 with Fulvestrant Combination Escalation

PF-07220060 with Letrozole Combination Expansion

PF-07220060 with fulvestrant Combination Expansion

PF-07220060 with enzalutamide Combination Expansion

PF-07220060 with fulvestrant combination dose expansion

PF-07220060

Enzalutamide

Pfizer CT.gov Call Center

This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.

The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide.

In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).

In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A.

Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC.

Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively.

Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide.

The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants.

The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.

Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors

A PHASE 1/2A STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C, 1F)

vital signs and heart rate corrected QT interval

Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D)

Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1E)

Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

Per RECIST v1.1 (Part 1 A-E; Part 2B and 2C); per PCWG3 (Part 1F and Part 2D)

Peak and trough concentration (Parts 2B, 2C, 2D)

time to functional status deterioration by FACT-P (Part 2D)

Pfizer

Oral, ribociclib 600 mg x 1 a day, 21 days on 7 days off

Ribociclib Oral 600 mg x 1 a day 21 days on 1 week off in 28 days cycles

Ribociclib

Daniela Katz, M.D

Sharona Ben Ami

Daniela Katz, MD

The purpose of this study is to determine whether ribociclib are effective and safe in the treatment of progressive well/dedifferentiated liposarcoma (WDL/DDL).

The expected duration of this study is 36 months (24 months accrual period and 12 month follow up period). Enrollment into the screening or treatment phase of the study will be stopped when the actual subject numbers have been achieved.

This single arm single institution, open label, prospective, phase II trial will evaluate the efficacy and safety of oral 600mg/daily in 28 day cycles of ribociclib in advanced well-differentiated liposarcoma (WDL) and de-differentiated liposarcoma (DDL) patients. Number of patients in the study will reflect the reconciliation between statistical requirements and incidence.

Treatment will continue until disease progression, development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient or investigator decision.

All screening requirements must be completed within 28 days of the visit (except for CDK4/6 amplification and pRb, p16 and cyclin D staining status which may be completed in advance). Patients will be examined on cycle 1 day-1 and every 2 weeks, including complete blood count (CBC) and chemistry, for the first 8 weeks of treatment, and thereafter every month until disease progression. CT/MRI imaging (contrast) will be performed every 8 weeks for response evaluation. Clinical benefit as well as individual categories of response (complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be determined using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST). Response duration endpoints, including PFS, PFS at 12 weeks and OS will be assessed using the Kaplan-Meier method. Toxicity (AEs) will be recorded using the NCI- Common Toxicity Criteria for Adverse Effects v 4.03 (NCI-CTCAE). Screening procedures will include medical history, physical examination, blood test, baseline CT/MRI imaging and formalin-fixed tissue submission for FoundationOne mutational analysis.

A Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma

A Phase II Single Arm Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well-Differentiated or Dedifferentiated Liposarcoma

PFS will be computed from the date of start of treatment to the first documented date of progression or the date of death, due to any cause assessed by investigator.

Number of total patients who are PFS at 12 weeks of treatment

will be computed from the date of start of treatment to the date of death, due to any cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up

Assaf-Harofeh Medical Center

Symptoms and General Pathology

Kidney Diseases

Recurrence

Hypoxia

Carcinoma, Renal Cell

Urologic Neoplasms

Urologic Diseases

Kidney Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Pharmaceutical Solutions

Antibodies

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Immunoglobulins

Immunoglobulin G

Palbociclib

Immunoglobulins, Intravenous

Protein Kinase Inhibitors

Lead-in Doublet assesses safety of oral dosing NKT2152 at increasing dosage levels in combination with palbociclib to determine a recommended dose for expansion (RDE).

Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab

Subjects randomized to Arm 1 will receive the Doublet combination (NKT2152 in combination with palbociclib) to provide an assessment of anti-tumor activity and to determine the RP2D.

Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.

NKT2152

a cyclin-dependent kinases (CDK) 4 and 6 inhibitor

palbociclib

an immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1; a solution for injection for subcutaneous administration

sasanlimab

Joanna Dojillo, M.Sc.

Sponsor Contact

Katie O'Neil

Rana McKay, MD

Rachel Springdorf

Ashley Matza-Wambaja

David VanderWelle, MD

Elena Stratis

Meredith Flynn

Toni Choueiri, MD

Cherie Donze

Ulka Vaishmpayan, MD

Tiffiny Bradley

Hanna Kurz

Ralphe Hauke, MD

Jodi-Ann Powell

Martin Voss, MD

Amy Rowell

Andrea Flaten

Hans Hammers

Sydney Sanders

Alexandra Cash

Robert Dreicer, MD

The goal of the Lead-in phase of the study is to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy. The goal of the Expansion phase of the study is to evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy.

This is a Phase 2 open-label, multicenter, global study of NKT2152. This study is designed as two phases: a Lead-in phase and an Expansion phase. Patients must be 18 years or older, with advanced or metastatic clear cell renal cell carcinoma (ccRCC). Eligible patients must have progressed or relapsed after at least 1 prior anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) systemic therapy and 1 immune checkpoint inhibitor (ICI) for advanced or metastatic ccRCC alone or in combination.

The Lead-in phase is designed as a dose escalation phase to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy.

The subsequent Expansion phase will evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy.

Lead-in/Dose Escalation (doublet \& triplet combination) and Dose Expansion (doublet \& triplet combination)

Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)

A Phase 2 Trial to Evaluate the Safety and Efficacy of NKT2152 in Combination With Palbociclib (Doublet) and With Palbociclib and Sasanlimab (Triplet) in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

IPD are not planned to be shared at this time

DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.

ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression or death.

Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first.

TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.

OS defined as the time from the date the participant started study drug to death for any reason.

CBR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) or a stable disease (SD) of 8 weeks or longer based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.

Maximum observed plasma concentration (Cmax) of NKT2152

Time to maximum observed plasma concentration of NKT2152 (Tmax)

Observed trough concentration of NKT2152 (Ctrough)

Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)

Maximum observed plasma concentration (Cmax) of palbociclib

Time to maximum observed plasma concentration of palbociclib (Tmax)

Observed trough concentration of palbociclib (Ctrough)

Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)

Observed trough concentration of sasanlimab (Ctrough)

Maximum observed plasma concentration (Cmax) of sasanlimab

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors	NCT04557449	Liposarcoma CRC Prostate Cancer Breast Neoplasm... Adenocarcinoma ... Solid Tumors	PF-07220060 Letrozole Fulvestrant Midazolam Enzalutamide	18 Years -	Pfizer
A Study Assessing Efficacy & Safety of Ribociclib in Patients With Advanced Well/Dedifferentiated Liposarcoma	NCT03096912	Liposarcomas, D... Liposarcoma - W... Liposarcoma; Mi... Soft-Tissue Sar...	Ribociclib	18 Years -	Assaf-Harofeh Medical Center
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors	NCT04557449	Liposarcoma CRC Prostate Cancer Breast Neoplasm... Adenocarcinoma ... Solid Tumors	PF-07220060 Letrozole Fulvestrant Midazolam Enzalutamide	18 Years -	Pfizer
Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)	NCT05935748	ccRCC Clear Cell Rena... Kidney Cancer Kidney Neoplasm... Renal Cancer Renal Neoplasms Recurrent Renal... Metastatic Rena... Refractory Rena... Advanced Renal ... Carcinoma Neoplasms Carcinoma, Rena... Neoplasms, Glan... Neoplasm by His... Adenocarcinoma Urologic Neopla... Urogenital Neop... Neoplasms by Si... Kidney Diseases Urologic Diseas...	NKT2152 palbociclib sasanlimab	18 Years -	NiKang Therapeutics, Inc.

Spots Global Cancer Trial Database for cdk4 inhibitor