Palbociclib and Sasanlimab for the Treatment of Advanced Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (pRCC)

Last updated: July 16, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Recruiting

Phase

1/2

Condition

Carcinoma

Urothelial Cancer

Urothelial Tract Cancer

Treatment

Sasanlimab

Palbocicilib

Clinical Study ID

NCT05665361
10000666
000666-C
  • Ages 18-100
  • All Genders

Study Summary

Background:

Kidney cancer is the 12th leading cause of cancer-related death in the United States. Some kidney tumors do not respond well to current treatments. Better treatments are needed.

Objective:

To test a pair of drugs (sasanlimab and palbociclib) in people with kidney cancers.

Eligibility:

People aged 18 years and older with kidney cancer; specifically, clear cell renal cell carcinoma (ccRCC) or papillary renal cell carcinoma (pRCC).

Design:

Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan and a test of their heart function. They may have a biopsy; that is, a sample of tissue will be cut from the tumor.

Participants will be treated in 28-day cycles for up to 2 years.

Palbociclib is a pill taken by mouth. Participants will take this drug once a day for 21 days during each 28-day treatment cycle. They will write down the dates and times they take these pills in a diary.

Sasanlimab is an injection under the skin. Participants will receive this injection on the first day of each treatment cycle.

Imaging scans and blood tests will be repeated throughout the treatment. Tumor biopsies may be repeated up to 3 times; these biopsies are optional.

Participants will have follow-up visits every month for 3 months after treatment ends. They will continue to have imaging scans every 3 months; these scans may be done close to home. The results can be sent to researchers.

Participants will remain in the study up to 6 years.

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:

  • Cytologically or histologically confirmed clear cell renal cell carcinoma (presenceof a clear cell component) (ccRCC) (Cohort 1) or papillary renal cell carcinoma (pRCC) (presence of a papillary component) (Cohort 2)

  • Participants must have advanced RCC with at least one measurable lesion as outlinedin RECIST 1.1.

  • Participants with ccRCC (Cohort 1) must have received checkpoint inhibitor therapyand must have received or been ineligible to receive a VEGF pathway antagonist (as asingle agent or as part of a combination)

  • Participants with pRCC (Cohort 2) can be treatment-na(SqrRoot) ve or have previouslyreceived systemic treatment for pRCC

  • Age >= 18 years

  • ECOG performance status <= 1

  • Adequate hematologic function at screening, as follows:

  • Absolute neutrophil count (ANC) >= 1,000/microliter

  • Hemoglobin (Hb) >= 9 g/dL with no blood transfusion within 2 weeks prior totreatment initiation

  • Platelets >= 100,000/microliter

  • Adequate renal and hepatic function at screening, as follows:

  • Serum creatinine <= 1.5 x upper limit of normal (ULN) OR, if >1.5x ULN,creatinine clearance (CrCl) >= 30 mL/min/1.73 m^2 (calculated CrCl (CKD-EPI orcalculated eGFR provided by laboratory))

  • Total bilirubin <= 1.5 x ULN OR in participants with known or suspectedGilbert's syndrome, total bilirubin <= 3.0 x ULN

  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 xULN, (unless liver metastases are present, then values must be <= 5 x ULN)

  • Participants serologically positive for hepatitis C virus (HCV) are eligible if HCVviral load is undetectable

  • Participants serologically positive for human immunodeficiency virus (HIV) areeligible if they are on stable antiretroviral therapy for at least 4 weeks beforetreatment initiation, have no reported opportunistic infections or Castleman sdisease within 12 months prior to treatment initiation, have a viral load that isundetectable by quantitative polymerase chain reaction (PCR) and CD4 count >= 200cells per cubic millimeter

  • Participants with brain metastasis are eligible if at least 4 weeks status postradiotherapy or surgery before treatment initiation with no evidence of progressionor associated symptoms

  • Women of child-bearing potential (WOCBP) must agree to use one (1) highly effectivemethod of contraception (e.g.,hormonal, intrauterine device (IUD), surgicalsterilization) prior to study entry, for the duration of study therapy, and for upto 6 months following the last dose of any study agent(s). Women must refrain fromdonating eggs during this same period. NOTE: WOCBP is defined as any female who hasexperienced menarche and who has not undergone successful surgical sterilization orwho is not postmenopausal.

  • Men with female partners of reproductive potential and pregnant partners arerequired to use a condom (even after vasectomy), during treatment and for at least 6months after the final dose and must refrain from donating sperm during this sameperiod.

  • Breastfeeding participants must be willing to discontinue breastfeeding from studyenrollment through 6 months after study treatment discontinuation

  • Participants must be able to understand and be willing to sign a written informedconsent document

Exclusion

EXCLUSION CRITERIA:

  • Prior treatment for RCC with chemotherapy, hormonal therapy, immunotherapy,treatment with an experimental agent, and/or radiation therapy within 4 weeks or 5halflives, whichever is shorter, prior to treatment initiation

  • More than two prior lines of systemic therapy in the metastatic setting

  • Participants who have wound dehiscence from prior surgeries

  • Active inflammatory bowel disease, chronic diarrhea, gastrointestinal malabsorption,gastrointestinal anastomosis, or any other condition that might affect theabsorption of palbociclib

  • History of allergic reactions attributed to compounds of similar chemical orbiologic composition to the study agents

  • Prior history of grade >=3 immune-related adverse event(s) with checkpoint inhibitortherapy. Note: participants who had endocrine toxicity of grades 3 or 4 are eligible

  • An active autoimmune disease. Note: participants with type 1 diabetes, eczema,vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease, adrenal insufficiencyon systemic oral corticosteroid therapy (<= the equivalent of prednisone 10 mg/day)or other mild autoimmune disorders not requiring immunosuppressive treatment areeligible.

  • Participants receiving systemic corticosteroids at doses equivalent > 10 mg/daily ofprednisone, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil,sirolimus, thalidomide, or anti-tumor necrosis factor [anti-TNF] agents. Note:participants on steroids through a route known to result in minimal systemicexposure (topical, intranasal, intro-ocular, or inhalation) are eligible

  • Prior allogeneic/autologous bone marrow or solid organ transplant

  • Participants with current or past hepatitis B (HBV) infection

  • Participants with a history of interstitial lung disease, non-infectiouspneumonitis, or active/latent pulmonary tuberculosis (TB)

  • Participants taking medications that are strong inhibitors or inducers of CYP3A (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers#table3-2) within 21 days or 5half-lives of the agent (whichever is shorter) prior to initiation of study therapy

  • Participants taking any herbal supplements within 14 days prior to initiation ofstudy therapy

  • History of a non RCC malignancy within 2 years of treatment initiation except forthe following: adequately treated localized skin cancer, ductal carcinoma in situ,cervical carcinoma in situ, superficial bladder cancer, or other malignancy whichdoes not require treatment at the current time per Standard of Care

  • Pregnant women (confirmed by <=-HCG serum pregnancy test performed at screening)

  • Uncontrolled intercurrent illness that would limit compliance with studyrequirements evaluated by history, physical exam, and chemistry panel

Study Design

Total Participants: 100
Treatment Group(s): 2
Primary Treatment: Sasanlimab
Phase: 1/2
Study Start date:
April 24, 2024
Estimated Completion Date:
June 01, 2027

Study Description

Background:

  • Kidney cancer is the 8th most common malignancy and 12th leading cause of cancer-related death in the United States. It is estimated that there will be 79,000 new cases of kidney cancer diagnosed in 2022, resulting in 13,920 deaths. Despite a steady increase in the incidence of renal cell cancer (RCC) over the past 3 decades, there has been an improvement in observed 5-year survival rates

  • Most patients with advanced clear cell RCC are treated with immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) and/or the CTLA4 axis and agents targeting the vascular endothelial growth factor (VEGF) pathway. There is a paucity of options for patients who have progressed on these therapies. There is currently no widely accepted standard for patients with papillary RCC, although some patients may benefit from agents such as cabozantinib or the combination of bevacizumab and erlotinib

  • Preclinical data suggest that inhibitors of CDK 4/6 might be active in kidney cancer and that these agents might act synergistically with PD-1 checkpoint inhibitors in a variety of preclinical models

  • Palbociclib is a highly selective, reversible oral inhibitor of cyclin-dependent kinases (CDK) 4 and 6. Inhibition of CDK 4/6 blocks DNA synthesis by prohibiting the progression of the cell cycle from G1 to the S phase. Data from nonclinical studies indicate that palbociclib may have cytostatic effects on tumor cells

  • Sasanlimab is an investigational humanized immunoglobulin G4 monoclonal antibody that binds PD-1 and blocks its interaction with its ligands, programmed death-ligand 1 and 2 (PD-L1) & (PD-L2). It presents the distinct characteristic that it can be administered subcutaneously on a monthly basis whereas approved and other available anti-PD-1/PDL1 therapies currently are administered intravenously. In animal models, it demonstrated high-affinity interaction with PD 1 and was associated with a significant delay in the growth of murine MC-38 colorectal tumors implanted in hu-PD-1 knock-in mice

Objectives:

  • Phase I: To determine recommended phase II dose (RP2D) of palbociclib in combination with sasanlimab

  • Phase II: To determine the overall response rate (ORR) defined as partial response (PR) + complete response (CR) of the RP2D of the combination of palbociclib and sasanlimab in participants with advanced ccRCC (Cohorts 1a and 2a) and advanced pRCC (Cohorts 1b and 2b) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Eligibility:

  • Age 18 years or older

  • Participants with histologically or cytologically confirmed advanced ccRCC or pRCC

  • Participants must have measurable disease per RECIST 1.1

  • ECOG performance status <= 1

  • Adequate organ function as defined by the liver, kidney, and hematologic laboratory testing

  • Participants with ccRCC must have received checkpoint inhibitor therapy and must have received or been ineligible to receive a VEGF pathway antagonist (as a single agent or as part of a combination)

  • Participants with pRCC can be treatment-na(SqrRoot) ve or have previously received systemic treatment for pRCC.

  • No more than two prior lines of therapy in the metastatic setting.

Design:

  • The proposed study is an open label, phase I/II study of palbociclib in combination with sasanlimab

  • Participants will be enrolled simultaneously into Cohort 1a (ccRCC) and Cohort 1b (pRCC) and start treatment in cycles consisting of 28 (+/- 5) days

  • Initially, 6-18 participants from Cohort 1a and/or Cohort 1b will be enrolled into Phase I to estimate RP2D. If RP2D is estimated, we will continue enrollment as planned into Phase II, if not, we will submit amendment with updated dosing

  • Following the Phase I, the first 9 participants from each pair of Cohorts (1a+2a) and (1b+2b) enrolled at the RP2D of palbociclib and sasanlimab in Phase I and Phase II will be evaluated separately for response. If among these 9 participants from pair of Cohorts (1a+2a) and (1b+2b), no more than 1 objective response defined as CR+PR is seen, then no further participants will be enrolled in Cohort 2a or 2b

Connect with a study center

  • National Institutes of Health Clinical Center

    Bethesda, Maryland 20892
    United States

    Active - Recruiting

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