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KEYNOTE-905/EV-303 (NCT03924895), a phase 3, open-label, randomized trial, evaluated perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) compared with surgery alone in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or declined cisplatin-based chemotherapy.

Presented by Prof. Christof Vulsteke at the ESMO Congress 2025, the study demonstrated that adding EV + pembro to radical cystectomy with pelvic lymph node dissection resulted in significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR). These findings mark a major advance for cisplatin-ineligible MIBC, establishing a potential new perioperative standard of care.

Background

Radical cystectomy with pelvic lymph node dissection (RC + PLND) remains the standard of care for patients with muscle-invasive bladder cancer. However, nearly half of these patients are ineligible for cisplatin-based chemotherapy due to renal dysfunction, frailty, or comorbidities, leaving a substantial population without effective perioperative options.

Previous studies have shown limited benefit from surgery alone in this setting, underscoring the unmet need for alternative strategies. Enfortumab vedotin, an antibody–drug conjugate targeting Nectin-4, combined with pembrolizumab, has demonstrated potent antitumor activity and a favorable safety profile in metastatic urothelial cancer, providing a strong rationale for evaluation in the perioperative context.

Methods

KEYNOTE-905/EV-303 is a randomized, open-label, phase 3 trial that enrolled adults with MIBC (T2–T4aN0M0 or T1–T4aN1M0) who were cisplatin-ineligible per Galsky criteria or declined cisplatin.
Participants were randomized 1:1 to receive:

• EV + pembro arm: Three cycles of EV (1.25 mg/kg on days 1 and 8) plus pembrolizumab (200 mg every three weeks) before RC + PLND, followed by six additional EV cycles and 14 cycles of pembrolizumab postoperatively.
• Control arm: RC + PLND alone, with adjuvant nivolumab permitted when clinically indicated.

The primary endpoint was event-free survival (EFS) by blinded independent central review (BICR).Key secondary endpoints included overall survival (OS), pathologic complete response (pCR), and safety.

Timeline of study development:

• The study initiated in 2019 with two treatment arms—perioperative pembrolizumab + RC + PLND vs RC + PLND alone—randomized 1:1.
• In 2020, a third arm was added, introducing perioperative EV + pembro + RC + PLND, changing the randomization to 1:1:1.
• By 2022, the design evolved: the pembrolizumab-alone arm was discontinued, and randomization was updated to 1:1 between EV + pembro + RC + PLND (EV + pembro arm) and RC + PLND (control arm).
• The inclusion criteria were expanded to include patients who were cisplatin-eligible but declined cisplatin, broadening the real-world relevance of the study population.
• Adjuvant nivolumab was permitted in the control arm per local guidelines.

Results

A total of 344 participants were randomized between December 2020 and June 2024 (170 to EV + pembro; 174 to control). Over 80% were cisplatin-ineligible, and the median follow-up was 25.6 months (range 11.8–53.7).The combination regimen produced statistically significant and clinically meaningful improvements across all efficacy endpoints:

• Event-Free Survival (EFS): Median EFS was not reached with EV + pembro versus 15.7 months with control (HR 0.40; 95% CI 0.28–0.57; P<0.0001). At one years, EFS rates were 77.8% vs 55.1%, respectively and at two years, 74,7% vs 39,4%

• Overall Survival (OS): Median OS was not reached with EV + pembro versus 41.7 months with control (HR 0.50; 95% CI 0.33–0.74; P=0.0002). The 12-month OS rates were 86.3% vs 75.7%, and the 24-months OS rates were 79,7% vs 63,1%

• Pathologic Complete Response (pCR): 57.1% with EV + pembro vs 8.6% with control, an absolute difference of 48.3% (95% CI 39.5–56.5; P<0.0001).

Safety:

Treatment-emergent adverse events (TEAEs) occurred in nearly all patients (100% in EV + pembro vs 64.8% in control). Grade ≥3 events were reported in 71.3% and 45.9%, respectively. The most frequent grade ≥3 adverse events of special interest were severe skin reactions (11.4%) related to pembrolizumab and cutaneous toxicity (10.8%) associated with enfortumab vedotin.

Despite the high incidence of AEs, the safety profile remained manageable and consistent with prior studies, and no new safety signals were identified.

Conclusions

The KEYNOTE-905/EV-303 trial demonstrated that adding perioperative enfortumab vedotin plus pembrolizumab to standard surgery significantly improved event-free survival, overall survival, and pathologic complete response rates in patients with cisplatin-ineligible MIBC.

These findings establish EV + pembrolizumab as the first perioperative regimen to improve outcomes versus RC + PLND alone in this population, offering a potential new standard of care.

You can read the full abstract here.

Red Cat Holdings, Inc. (NASDAQ:RCAT) is one of the stocks Jim Cramer was focused on recently. When a caller asked about the stock during the lightning round, Cramer said:

“Okay, so this is a Ben Stoto favorite, not really. It’s a drone company. We are on the fence about buying drone companies that aren’t making money.”

Pixabay/Public Domain

Red Cat Holdings, Inc. (NASDAQ:RCAT) develops drone systems and control technologies for military, government, and commercial use. During the February 18 episode, Cramer mentioned the stock and remarked:

“This one just happens to be a personal favorite of our chief scientist, Ben Stoto. We talk about Red Cat a lot. It’s a data analytics company, and you know what? I’m going to tell you, you can buy it. You really can. Because if it doubled, you’d feel like an idiot for not buying Red Cat.”

It is worth noting that since the above comment was made, the company’s stock gained around 65%.

While we acknowledge the potential of RCAT as an investment, we believe certain AI stocks offer greater upside potential and carry less downside risk. If you’re looking for an extremely undervalued AI stock that also stands to benefit significantly from Trump-era tariffs and the onshoring trend, see our free report on the best short-term AI stock.

READ NEXT: 30 Stocks That Should Double in 3 Years and 11 Hidden AI Stocks to Buy Right Now.

Disclosure: None. This article is originally published at Insider Monkey.

Futu Holdings (NasdaqGM:FUTU) shares have seen a steady climb this year, with the stock up over 100% year-to-date. Many investors are now reviewing its recent performance and growth numbers for insights into what might come next.

See our latest analysis for Futu Holdings.

Futu Holdings has enjoyed sustained momentum, with a 105.8% year-to-date share price return. This reflects renewed investor confidence and optimism around its growth story. Over the past year, its total shareholder return reached 79.4%, underscoring long-term performance beyond just recent gains.

If you’re weighing what else might be showing breakout momentum, this is a great moment to broaden your search and discover fast growing stocks with high insider ownership

With shares surging so impressively, the central question becomes whether Futu Holdings is still undervalued at current levels, or if the market is already accounting for the company’s future growth potential and leaving little room for upside.

Compared to Futu Holdings’ last close price of $163.53, the most widely followed narrative estimates a fair value of $207.27. The picture that emerges is of a company with catalysts that some see as transformative, and a valuation that challenges the market’s current view.

The rapid growth in funded accounts, especially from international markets such as Singapore, the U.S., Malaysia, and Japan, signals ongoing global expansion and diversification of Futu’s user base. This positions the company to capture rising middle-class wealth and digital financial adoption in Asia, supporting long-term revenue and AUM growth.

Read the complete narrative.

What is driving that bold upside call? This narrative is built on expectations of relentless customer growth, a resilient business model, and margin strength usually reserved for industry leaders. The surprising mix of ambitious projections and global expansion creates a valuation thesis you will not want to miss.

Result: Fair Value of $207.27 (UNDERVALUED)

Have a read of the narrative in full and understand what’s behind the forecasts.

However, risks remain, as heightened competition in key Asian markets and regulatory hurdles could quickly turn investor optimism into caution for Futu Holdings.

Find out about the key risks to this Futu Holdings narrative.

While many focus on analyst price targets, compare Futu Holdings’ current price-to-earnings ratio of 22.4x against the industry average of 25.4x and a peer average of 22.2x. However, the fair ratio for Futu is estimated at 21.4x, suggesting that shares could be slightly expensive. This is an important detail for those weighing potential returns or risks.

See what the numbers say about this price — find out in our valuation breakdown.

If the narrative above doesn’t reflect your perspective, why not take a closer look at the figures yourself and craft your own in just a few minutes using Do it your way

A good starting point is our analysis highlighting 3 key rewards investors are optimistic about regarding Futu Holdings.

Don’t let great opportunities pass you by. Expand your watchlist with high-potential stocks you may have missed. Use these targeted screens to stay one step ahead:

This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include FUTU.

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