Kidney Cancer Clinical Trial

Dose Finding Study of CBM588 in Combination With Nivolumab/Ipilimumab in Advanced Stage Renal Cell Carcinoma

Summary

This is a single arm open-label phase 1 study evaluating the safety and efficacy of escalating doses of CBM588 in combination with nivolumab and ipilimumab. A standard 3+3 dose escalation schema will be used initially to assess the maximum tolerated dose (MTD) followed by a dose expansion of 10 patients at the MTD to further evaluate safety and efficacy.

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Full Description

This protocol is a phase I open-label, single institution, dose escalation study designed to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of CBM588 in combination with nivolumab and ipilimumab in patients with previously untreated advanced or metastatic renal cell carcinoma.

The dose escalation phase of the trial will be conducted using a standard 3+3 dose-escalation design to determine the MTD or RP2D. In addition to prespecified dose escalation levels of CBM588, which will be given twice a day continuously, all patients will receive standard of care treatment with nivolumab (3 mg/kg IV every 3 weeks for 4 cycles, followed by 480 IV every 4 weeks) and ipilimumab (1 mg/kg IV q3wks for 4 cycles. At each dose level 3-6 patients will be enrolled based on the decision rule of 3+3 dose-escalation design. Initially, 3 patients are enrolled into the starting dose cohort. If no dose limiting toxicity (DLT) is observed in any of these subjects, the trial proceeds to enroll subjects into the next higher dose cohort. If one subject develops a dose limiting toxicity (DLT) at a specific dose, an additional three subjects are enrolled into that same dose cohort. Development of DLTs in more than 1 of 6 subjects in a specific dose cohort suggests that the MTD has been exceeded, and no further dose escalation is pursued.

Once the MTD is determined, a dose expansion phase will be conducted by enrolling 10 additional patients at the MTD to further evaluate that dose for safety and clinical efficacy endpoints.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Informed Consent and Willingness to Participate

Documented informed consent of the participant and/or legally authorized representative.
Agreement to allow the use of archival tissue from diagnostic tumor biopsies Age Criteria, Performance status
ECOG ≤ 2
Age ≥ 18 years Nature of Illness and Illness Related Criteria
Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component or sarcomatoid component.
Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with intermediate- or poor-risk disease by IMDC criteria

No prior systemic therapy for RCC with the following exception:

i. One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy.

Measurable disease by RECIST 1.1
Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy Clinical Laboratory and Organ Function Criteria
Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support.
White blood cell count ≥ 2500/µL.
Platelets ≥ 100,000/µL without transfusion.
Hemoglobin ≥ 8 g/dL
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases.
Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
Serum albumin ≥ 2.8 g/dl.
(PT)/INR or partial thromboplastin time (PTT) test < 1.3 x the laboratory ULN
Serum calculated creatinine clearance ≥ 50mL/min using the Cockcroft-Gault equation: i. Males: (140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72) ii. Females: [(140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85 Contraception
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab for women with childbearing potential, and 7 months after the last dose of nivolumab for men.
Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating (FSH) level > 40 mIU/mL to confirm menopause).

Exclusion Criteria:

Prior and concomitant therapies and supplements

Prior treatment with ipilimumab and/or nivolumab
Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment. Other illnesses or conditions
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.

Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis).

Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.

Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.

The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: i. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed. ii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection. iii. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. iv. Malabsorption syndrome. v. Uncompensated/symptomatic hypothyroidism. vi. Moderate to severe hepatic impairment (Child-Pugh B or C). vii. Requirement for hemodialysis or peritoneal dialysis. viii. History of solid organ or allogenic stem cell transplant ix. Other clinically significant disorders that would preclude safe study participation: 1). Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions:

Type 1 diabetes mellitus.
Hypothyroidism only requiring hormone replacement.
Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment.
Conditions not expected to recur in the absence of an external trigger.
Pregnant or lactating females.
Inability to swallow tablets/capsules or unwillingness or inability to receive IV administration.

Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies.

Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded.

Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
Exclusion of subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.
Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures. Noncompliance
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Study is for people with:

Kidney Cancer

Phase:

Phase 1

Estimated Enrollment:

28

Study ID:

NCT06414642

Recruitment Status:

Recruiting

Sponsor:

Osel, Inc.

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There is 1 Location for this study

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City of Hope Medical Center
Duarte California, 91010, United States More Info
Alexander Chehrazi-Raffle, M.D.
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Kidney Cancer

Phase:

Phase 1

Estimated Enrollment:

28

Study ID:

NCT06414642

Recruitment Status:

Recruiting

Sponsor:


Osel, Inc.

How clear is this clinincal trial information?

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