Ribociclib + PDR001 in Breast Cancer and Ovarian Cancer

NCT03294694 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 17-285
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

This clinical trial is studying the drug Ribociclib (LEE011) in combination with an immunotherapy drug called PDR001 (a therapy that uses the body's own immune system to control cancer) as a possible treatment for metastatic hormone-receptor-positive (HR+), HER2-negative breast cancer (in combination with fulvestrant) or metastatic epithelial ovarian cancer. The names of the medications involved in this study are:

• Ribociclib (LEE011)
• PDR001
• Fulvestrant

Conditions

Metastatic Hormone-Receptor-Positive (HR+) Breast Cancer; HER2-Negative Breast Cancer; Metastatic Epithelial Ovarian Cancer

Keywords

Metastatic Hormone-Receptor-Positive (HR+) Breast Cancer; HER2-Negative Breast Cancer; Metastatic Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Cohort A: MTD/RP2D of the Combination of Ribociclib + PDR001

  Toxicity will be graded according to NCI CTCAE, Version 4.0.

  4 weeks

• Cohort B: MTD/RP2D of the Combination of Ribociclib + PDR001 + Fulvestrant

  Toxicity will be graded according to NCI CTCAE, Version 4.0.

  4 weeks

Secondary Outcomes (2)

• Number of Participants with Adverse Events

  All participants will be evaluable for toxicity from the time of their first treatment with any study agent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Objective Response Rate

  2 Years

Study Arms (2)

Ribociclib and PDR001 (Cohort A)

EXPERIMENTAL

* The treatment regimen is defined as ribociclib + PDR001. * Treatment will be administered on an outpatient basis. * The study will use a 3 + 3 dose escalation design to determine the MTD/RP2D. * Three to six evaluable patients will be enrolled in each cohort in the dose escalation phase. * Once the RP2D of the combination of ribociclib + PDR001 is determined, there will be an expansion cohort. * Cohort A expansion will assess the combination of ribociclib + PDR001 in 12 patients with metastatic ovarian cancer.

Drug: Ribociclib; Drug: PDR001

Ribociclib, PDR001 and Fulvestrant (Cohort B)

EXPERIMENTAL

* The treatment regimen is defined as ribociclib + PDR001 + fulvestrant . * Treatment will be administered on an outpatient basis. * There will be a safety run-in using the MTD/RP2D of ribociclib + PDR001 from Cohort A with the addition of fulvestrant in an initial 6-12 patients. * Once the safety of the combination of ribociclib + PDR001 + fulvestrant is established, there will be an expansion cohort. * Cohort B expansion will assess the combination of ribociclib + PDR001 + fulvestrant in 24 patients with hormone receptor-positive metastatic breast cancer (HR+ MBC).

Drug: Ribociclib; Drug: PDR001; Drug: Fulvestrant

Interventions

Ribociclib DRUG

Each treatment cycle lasts 28 days. Ribociclib, 1 time per day by mouth for 21 days, followed by 1-week of rest (28-day cycle)

Also known as: Kisqali, LEE011, LEE-011

Ribociclib and PDR001 (Cohort A); Ribociclib, PDR001 and Fulvestrant (Cohort B)

PDR001 DRUG

Each treatment cycle lasts 28 days. (PDR001) will be administered once every 28 days (by intravenous infusion) over about 30 minutes (or up to 2 hours, if necessary) for the first infusion and over about 30 minutes for all following infusions.

Ribociclib and PDR001 (Cohort A); Ribociclib, PDR001 and Fulvestrant (Cohort B)

Fulvestrant DRUG

Each treatment cycle lasts 28 days. Fulvestrant will be administered during Cycle 1 on days 1 and 15, and then on day 1 of each 28-day cycle thereafter.

Also known as: Faslodex, ICI 182,780, ZD9238

Ribociclib, PDR001 and Fulvestrant (Cohort B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A Dose Escalation (Ribociclib + PDR001) Eligibility can be found in Detailed Description Section
• Cohort B Safety Run-In (Ribociclib + PDR001 + Fulvestrant) Eligibility can be found in Detailed Description Section
• Cohort A Dose Expansion (Ribociclib + PDR001) Eligibility can be found in the Detailed Description Section
• Expansion Cohort B (Ribociclib + PDR001 + Fulvestrant Eligibility can be found in the Detailed Description Section
• ECOG Performance Status 0-1
• Participants must have normal organ and marrow function, as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total hemoglobin ≥ 9 g/dL (may be post-transfusion)
• total bilirubin ≤1.5 x institutional ULN (IULN)
• AST(SGOT)/ALT(SGPT) ≤2.5 × IULN or ≤5 × IULN for participants with liver metastases
• creatinine ≤1.5 x IULN or ≥ 60 ml/min/1.73m2 for subjects with creatinine levels above institutional normal
• INR ≤ 1.5
• estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 by either Cockcroft-Gaultor CKD-EPI
• baseline QTc ≤ 450 msec

You may not qualify if:

• Participants cannot have been treated on a prior interventional, investigational study within 2 weeks of the first dose of study treatment.
• Participants cannot receive treatment with any other investigational agents during protocol therapy.
• Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF) ≤2 weeks prior start of study drug. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment.
• History of severe hypersensitivity reactions to other mAbs
• Participants requiring chronic treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency within 7 days of treatment initiation. Topical, inhaled, nasal and ophthalmic steroids are allowed. Physiologic doses of steroids are acceptable.
• Participants receiving systemic treatment with any immunosuppressive medication (other than steroids as described above).
• Patient is currently receiving warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), coumadin or fondaparinux is allowed.
• Use of any live vaccines within 4 weeks of initiation of study treatment.
• Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
• Participants with active autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Presence of ≥ CTCAE grade 2 toxicity (CTCAE Grade 2 peripheral neuropathy and ototoxicity and any grade alopecia are allowed).
• Participants with uncontrolled intercurrent illness including, but not limited to:
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

ribociclib; spartalizumab; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Sara Tolaney, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 27, 2017
• Study Start: November 8, 2017
• Primary Completion: October 14, 2020
• Study Completion: October 14, 2020
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)