Pembrolizumab + Sacituzumab Govitecan for Urothelial Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Anti-PD(L)1 therapy

Must not be taking: Systemic immunosuppressive medication

Disqualifiers: Pregnancy, Breastfeeding, UGT1A1 deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 51

Duration: Up to 2 years

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares the effectiveness of two treatments, pembrolizumab and sacituzumab govitecan, against standard chemotherapy for treating urothelial cancer that has spread. Pembrolizumab, an immunotherapy, helps the immune system attack cancer cells, while sacituzumab govitecan combines an antibody with chemotherapy to target and kill cancer cells. The trial seeks participants with urothelial cancer that has advanced locally or spread to other parts of the body and who have previously received at least one line of therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must not be on systemic immunosuppressive medication, including high doses of steroids, at the time of randomization.

Is there any evidence suggesting that pembrolizumab and sacituzumab govitecan are likely to be safe for humans?

Research has shown that the combination of pembrolizumab and sacituzumab govitecan is generally well-tolerated by patients with advanced bladder cancer. In earlier studies, this combination proved effective for many patients. Most side effects were manageable and not too severe for most individuals.

One study found that some patients experienced more serious side effects, such as a significant drop in white blood cells, which can hinder infection-fighting ability. This occurred in about 36% of the patients. However, not everyone faced these more serious issues.

These findings suggest that while some risks exist, many patients can handle the treatment. It's important to weigh these risks against the potential benefits and discuss them with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab combined with sacituzumab govitecan for urothelial cancer because these treatments bring a fresh approach compared to standard chemotherapy options like carboplatin, cisplatin, and gemcitabine. Pembrolizumab is an immunotherapy that boosts the body's own immune system to fight cancer, while sacituzumab govitecan is an antibody-drug conjugate that targets and delivers chemotherapy directly to cancer cells, minimizing harm to healthy cells. This combination could potentially offer a more effective and targeted attack on cancer cells, with the hope of improved outcomes and fewer side effects compared to traditional chemotherapy.

What evidence suggests that pembrolizumab and sacituzumab govitecan might be effective for urothelial cancer?

Research shows that combining pembrolizumab and sacituzumab govitecan may help treat urothelial cancer. In this trial, one group of participants will receive this combination. Earlier studies found that many patients experienced their cancer shrinking or halting its growth with this treatment. Most patients found the side effects manageable. Pembrolizumab aids the immune system in attacking cancer cells, while sacituzumab govitecan delivers chemotherapy directly to them. These findings suggest that this combination might be more effective than traditional chemotherapy for advanced urothelial cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Monika Joshi

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with advanced urothelial cancer that has spread, who have tried some treatments like anti-PD(L)1 therapy and possibly chemotherapy. They should be able to perform daily activities (ECOG 0-2), have measurable disease by certain criteria, and may have had up to two or three prior systemic therapies depending on specific genetic alterations in their tumors.

Inclusion Criteria

I have previously been treated with enfortumab vedotin.

ANC ≥ 1,500/uL

Patient must have Bellmunt score of 0-2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either TPC chemotherapy or the combination of pembrolizumab and sacituzumab govitecan. Cycles repeat every 21 days.

Up to 2 years

Visits every 21 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Follow-up at 30 days post-treatment, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview The study tests pembrolizumab combined with sacituzumab govitecan against standard chemotherapies (cisplatin, carboplatin, gemcitabine, docetaxel or paclitaxel). Pembrolizumab boosts the immune system's response to cancer while sacituzumab govitecan targets and kills tumor cells directly.

How Is the Trial Designed?

Group I: Arm II (pembrolizumab, sacituzumab govitecan) Experimental Treatment 6 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 and sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients additional undergo blood sample collection, and CT or MRI throughout the study.

Group II: Arm I (TPC chemotherapy) Active Control 9 Interventions

Patients receive TPC with carboplatin or cisplatin IV on day 1 and gemcitabine IV on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternately receive TPC with docetaxel IV on day 1 of each cycle or paclitaxel IV on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients additional undergo blood sample collection, and CT or MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02835

TROPHY-U-01 Cohort 3 | Journal of Clinical Oncology SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06524544

NCT06524544 | A Study Comparing the Combination of ... This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitecan to standard of care in treating patients with ...

3. blog-ecog-acrin.org blog-ecog-acrin.org/now-enrolling-ea8231-study-for-patients-with-bladder-cancer-that-has-progressed-following-treatment/

EA8231 Study for Patients With Bladder Cancer That Has ... The 5-year survival rate for patients with locally advanced disease is about 40%, and lower (9%) for metastatic disease. The KEYNOTE-045 phase 3 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12173038/

Real-world clinical outcomes of sacituzumab govitecan ... There are limited data regarding outcomes of SG in patients with urothelial cancer previously treated with EV. · In a large real-world cohort, SG ...

5. bcan.org bcan.org/clinicaltrials/a-study-comparing-the-combination-of-pembrolizumab-and-sacituzumab-govitecan-versus-standard-of-care-in-the-treatment-of-advanced-urothelial-cancer/

A Study Comparing the Combination of Pembrolizumab ... This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitecan to standard of care in treating patients with urothelial cancer ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38261969/

TROPHY-U-01 Cohort 3 - PubMed SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06524544

NCT06524544 | A Study Comparing the Combination of ... This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitecan to standard of care in treating patients with urothelial cancer ...

8. esmoopen.com esmoopen.com/article/S2059-7029(25)01174-3/fulltext

Real-world clinical outcomes of sacituzumab govitecan ... In a large real-world cohort, SG after EV resulted in limited efficacy: ORR 11%, mPFS 2.1 months and mOS 6.0 months. Grade 3-4 neutropenia rates were 36%.