Combination of Ipi/Nivo Plus Sacituzumab Govitecan in Metastatic Cisplatin Ineligible Urothelial Carcinoma Patients

NCT04863885 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-20943CA209-63Y
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see how well the study drugs called Ipilimumab plus Nivolumab (IPI-NIVO) work when added to another study drug called Sacituzumab Govitecan for people who have metastatic bladder cancer.

Conditions

Metastatic Urothelial Carcinoma

Keywords

mUC; Bladder cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose

  Determine the Maximum Tolerated Dose (MTD)/ Recommended Phase 2 dose (RP2D) of Sacituzumab Govitecan when combined with Ipilimumab and Nivolumab

  Up to 12 months

• Phase 2: Overall Response Rate

  Overall Response Rate (ORR) of Sacituzumab Govitecan with Ipilimumab and Nivolumab combination. ORR is defined as the rate of the best overall response as complete response (CR) or partial response (CR). OR will be summarized by the percentage of responses with a 95% confidence interval as calculated from Clopper-Pearson method.

  Up to 30 months

Secondary Outcomes (6)

• Phase 1: Overall Response Rate

  Up to 12 months

• Phase 1: Duration of Response (DOR)

  Up to 12 months

• Phase 1: Progression Free Survival (PFS)

  Up to 12 months

• Phase 2: Progression Free Survival (PFS)

  Up to 30 months

• Phase 2: Duration of Response (DOR)

  Up to 30 months

Study Arms (4)

Phase 1 Dose Level 1

EXPERIMENTAL

Participants will be treated at dose level 1: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 8 mg/kg IV will be administered days 1 and 8 every 3 weeks.

Drug: Ipilimumab; Drug: Nivolumab; Drug: Sacituzumab govitecan

Phase 1 Dose Level 2

EXPERIMENTAL

Participants will be treated at dose level 2: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 10 mg/kg IV will be administered days 1 and 8 every 3 weeks.

Drug: Ipilimumab; Drug: Nivolumab; Drug: Sacituzumab govitecan

Phase 1 Dose Level -1

EXPERIMENTAL

If dose reduction is indicated, participants will be treated at dose level -1: Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks. Sacituzumab Govitecan 6 mg/kg IV will be administered days 1 and 8 every 3 weeks

Drug: Ipilimumab; Drug: Nivolumab; Drug: Sacituzumab govitecan

Phase 2: Treatment at Maximum Tolerated Dose (MTD)

EXPERIMENTAL

Participants will be treated at with Ipilumumab 3mg/kg + Nivolumab 1mg/kg IV day 1 every 3 weeks for 4 cycles, followed by Nivolumab 360 mg every 3 weeks plus the maximum tolerated dose of Sacituzumab Govitecan days 1 and 8 every 3 weeks.

Drug: Ipilimumab; Drug: Nivolumab; Drug: Sacituzumab govitecan

Interventions

Ipilimumab DRUG

Participants will receive Ipilimumab 3 mg/kg

Also known as: Yervoy

Phase 1 Dose Level -1; Phase 1 Dose Level 1; Phase 1 Dose Level 2; Phase 2: Treatment at Maximum Tolerated Dose (MTD)

Nivolumab DRUG

Participants will receive Nivoumab 1mg/kg

Also known as: Opdivo

Phase 1 Dose Level -1; Phase 1 Dose Level 1; Phase 1 Dose Level 2; Phase 2: Treatment at Maximum Tolerated Dose (MTD)

Sacituzumab govitecan DRUG

Participants will be treated at 1 of 2 dose levels of Sacituzumab govitecan, either at 8 mg/kg, 10 mg/kg, or 6 mg/kg.

Also known as: Trodelvy

Phase 1 Dose Level -1; Phase 1 Dose Level 1; Phase 1 Dose Level 2; Phase 2: Treatment at Maximum Tolerated Dose (MTD)

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Able to understand and give written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants with histologically documented locally advanced or metastatic urothelial carcinoma. Upper and lower tract tumors are permitted and mixed histologies are permitted if urothelial carcinoma is the predominant histology (≥50%).
• Ineligiblity for cisplatin-based chemotherapy, defined by any of the following: (a) Creatinine clearance (CL) \<60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-Gault formula. (b) CTCAE v5.0 Grade \> 1 hearing loss (c) CTCAE v5.0 Grade \> 1 neuropathy (d) NYHA Class \> II cardiac dysfunction
• Adequate organ function laboratory values as defined per protocol
• Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: (a) Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). (b) Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. Female participants if sexually active must agree to use dual methods of contraception during the study and for a minimum period of 5 months after the last dose of study drug.

You may not qualify if:

• Women who are pregnant or lactating.
• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial treatment.
• Prior chemotherapy for metastatic urothelial carcinoma at any time in the patient's medical history.
• Small-cell carcinoma component
• Prior chemotherapy for localized urothelial carcinoma completed within 12 months before registration. Has received anti-PD-1/PD-L1 therapy previously, except if used in earlier stage urothelial carcinoma such as non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC) as neoadjuvant or adjuvant therapy and completed \>3 months prior to registration.
• Prior therapy with sacituzumab govitecan, irinotecan, or any topoisomerase I-containing regimen or antibody-drug conjugate
• Received radiation therapy for bone metastasis ≤2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
• Participants with Gilbert's disease.
• An active second malignancy. Note: Participants with a history of malignancy that has been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or subjects with surgically cured tumors with low risk of recurrence are allowed to- enroll.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids greater than 20 mg of prednisone daily for brain metastases (or the equivalent) for at least 7 days prior to trial treatment. All participants with carcinomatous meningitis are excluded regardless of clinical stability.
• Active cardiac disease as defined in protocol.
• Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) and participants with a history of bowel obstruction.
• Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of enrollment.
• Must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids ≤10 mg prednisone or equivalent daily are permitted for reasons outside of CNS disease provided the dose is stable for 4 weeks).

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

Ipilimumab; Nivolumab; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jingsong K Zhang, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

• Guru Sonpavde, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 28, 2021
• Study Start: April 30, 2021
• Primary Completion: September 12, 2025
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)