Immunotherapy Plus Capivasertib for Metastatic Bladder Cancer

NCT07793578 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SPLP-001-25FVA ORD
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

This study aims to determine whether adding an oral medication called Capivasertib to ongoing immunotherapy can enhance treatment responses in patients with advanced bladder cancer (aBC), as well as to evaluate the safety of this combination. Capivasertib is an anti-cancer drug approved by the U.S. Food and Drug Administration (FDA) for breast cancer, but it is not approved for aBC and, in this study, will be used as an investigational agent. Immunotherapy is FDA-approved for aBC, yet while some patients respond, others either do not benefit or develop resistance after an initial response. Previous research indicates that drugs similar to Capivasertib may increase the effectiveness of immunotherapy. Therefore, this study will enroll patients whose aBC no longer responds to immunotherapy, add Capivasertib to their treatment regimen, and monitor for improvements in immune response against aBC and any potential side effects associated with the combination therapy.

Conditions

Advanced Urothelial Carcinoma

Keywords

advanced urothelial carcinoma; immune checkpoint inhibitor; PI3K/AKT; capivaseretib

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  ORR is defined as the percentage of patients who have a partial or complete response at any time during the treatment of this trial.

  through study completion, an average of 1 year

Secondary Outcomes (5)

• Progression-free survival (PFS)

  through study completion, an average of 1 year

• Overall survival (OS)

  through study completion, an average of 1.5 year

• Disease control rate (DCR)

  through study completion, an average of 1 year

• Safety

  through study completion, an average of 1 year

• Tolerability

  through study completion, an average of 1 year

Study Arms (1)

treatment

EXPERIMENTAL

Patients will continue ICI treatment and capivasertib will be added

Drug: capivasertib

Interventions

capivasertib DRUG

Patients will continue their ICI treatment, with capivasertib added at a dose of 400 mg orally twice daily, administered on a schedule of 4 days on followed by 3 days off, continuously throughout the study period.

Also known as: Truqap

treatment

Eligibility Criteria

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

You may qualify if:

• Male or female patients are eligible
• Diagnosis of urothelial carcinoma, with mixed histology permitted:
• Histologically or cytologically confirmed advanced or recurrent urothelial carcinoma, OR
• Documented Stage IV disease (T4b, Any N, M0; any T, Any N, M1a-b), Stage IIIB (T1-T4a, N2-N3, M0), or a subset of Stage IIIA (T1-T4a, N1, M0)
• Genomic testing, including assessment for PIK3CA, AKT1, or PTEN alterations, must have been performed
• Patients must have stable disease or cancer progression after at least 12 weeks of Immune Checkpoint Inhibitors (ICI) or ICI-based therapy, per RECIST v1.1 guidelines
• Patients must have received prior enfortumab vedotin unless contraindicated
• Patients must be asymptomatic or minimally symptomatic from metastatic urothelial cancer
• Willingness to receive ICI in combination with capivasertib during the study is required. If cancer progressed on an ICI plus another anti-cancer drug(s) (e.g., pembrolizumab plus enfortumab vedotin), the additional drug(s) must be discontinued for at least 14 days, while ICI is continued, prior to starting capivasertib.
• Patients must have no or only minimal and stable adverse events from prior cancer-directed therapy, including ICI
• Measurable disease is required:
• X-rays, CT/MRI, or physical exams must have been performed within 28 days before starting study medications
• At least one measurable lesion per RECIST 1.1 must be present at baseline (≥10 mm in longest diameter, or lymph nodes with a short axis ≥15 mm, using CT or MRI; previously irradiated lesions are excluded)
• Tumor samples:
• Baseline biopsy prior to treatment is strongly recommended, unless it poses excessive risk

You may not qualify if:

• Patients who have undergone major surgery within 4 weeks, or major radiation therapy within 2 weeks, prior to starting treatment. Prior palliative radiotherapy is permitted if completed at least 48 hours before study entry
• Receipt of another investigational agent within the past 4 weeks. Participation in observational studies is allowed
• Persistent toxicities (CTCAE Grade ≥2) from previous anticancer therapy, except for alopecia. Patients with irreversible toxicity not reasonably expected to be exacerbated by study intervention (as deemed by the investigator, such as hearing loss) may be included.
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow capivasertib, or prior significant bowel resection that may impair adequate absorption, distribution, metabolism, or excretion of capivasertib.
• Active tuberculosis infection, as determined by clinical evaluation, imaging, or tuberculosis testing per local practice
• Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor
• Known or suspected hypersensitivity to study drugs or any of their components
• Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to study intervention Patients with previously treated CNS metastases may be eligible if they have recovered from acute effects of radiation or surgery, discontinued corticosteroids for at least 4 weeks, and are neurologically stable
• Diagnosis of any other malignancy within the past 3 years, except adequately treated basal or squamous cell skin cancer, other Stage 0 or 1 cancers, or incidental prostate cancer found at cystoprostatectomy
• Moderate to severe symptoms from metastatic cancer, including moderate to severe pain, impaired organ function, or spinal cord compression
• Active autoimmune disease likely to worsen with ICI therapy. Patients with vitiligo, psoriasis, or thyroid disorders controlled without immunosuppressive therapy are eligible
• Known severe hypersensitivity reactions (Grade \>3) to monoclonal antibodies, history of anaphylaxis, or uncontrolled asthma
• History or concurrent condition of interstitial lung disease or severely impaired lung function, as judged by the investigator
• Any of the following cardiac risks:
• Mean resting corrected QT interval (QTc) \>470 milliseconds (ms) from triplicate ECGs at screening

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

Location

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104-4551, United States

Location

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

Location

MeSH Terms

Interventions

capivasertib

Study Officials

• Chong-Xian Pan, MD PhD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chong-Xian Pan, MD PhD

CONTACT

(857) 203-6189; chong-xian.pan@va.gov

Chun Yang, PhD

CONTACT

(857) 736-5462; Chun.Yang@va.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: All patients will continue ICI treatment and capivasertib will be added to the ongoing ICI treatment

Study Record Dates

• First Submitted: August 19, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)