Exelixis to Webcast Fireside Chats as Part of Upcoming Investor Conferences in May and June

On May 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported that company management will participate in fireside chats at the following investor conferences in May and June (Press release, Exelixis, MAY 22, 2025, View Source [SID1234653301]):

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TD Cowen 6th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper): Exelixis is scheduled to present virtually at 2:30 p.m. ET / 11:30 a.m. PT on Tuesday, May 27.
William Blair 45th Annual Growth Stock Conference: Exelixis is scheduled to present at 11:00 a.m. ET / 10:00 a.m. CT / 8:00 a.m. PT on Tuesday, June 3 in Chicago.
Jefferies Global Healthcare Conference 2025: Exelixis is scheduled to present at 7:35 a.m. ET / 4:35 a.m. PT on Wednesday, June 4 in New York City.

To access the webcast links, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. Replays will also be available at the same location for at least 30 days.

Replimune Reports Fiscal Fourth Quarter and Year End 2025 Financial Results and Provides Corporate Update

On May 22, 2025 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, reported financial results for the fiscal fourth quarter and year ended March 31, 2025 and provided a business update (Press release, Replimune, MAY 22, 2025, View Source [SID1234653316]).

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"As we near our PDUFA date, our commercial organization is now fully hired and ready to execute our first launch in advanced melanoma," said Sushil Patel, Ph.D., CEO of Replimune. "We have a deep understanding of the market landscape, prescriber adoption and referral patterns, and a launch plan optimized for intra-tumoral delivery across all customer segments. We believe the opportunity for RP1 to help improve the lives of patients with advanced melanoma is significant. We estimate approximately 13,000 patients progress on or after PD-1 treatment annually in the U.S. with approximately 80% of these patients eligible for treatment with RP1. Importantly, these treatments will take place in the outpatient setting and not require hospitalization. We look forward to further discussing our commercial plans for RP1 and pipeline development for RP1 and RP2 at an investor day on June 24th."

Program Highlights & Milestones

RP1 (vusolimogene oderparepvec)

RP1 combined with Opdivo (nivolumab) in anti-PD1 failed melanoma
The FDA recently completed their late-cycle review and manufacturing inspections for the biologics license application, which remains on schedule ahead of a July 22, 2025 PDUFA date.
The FDA has indicated no advisory committee is planned.
The Company completed the build out of its commercial infrastructure, including the hiring and training of customer-facing teams. Distribution channels have been established and are ready to receive product, pending approval, and key state licensing is in place.
Enrollment is ongoing in the confirmatory Phase 3 trial, IGNYTE-3, with over 100 sites planned globally. This trial is expected to enroll 400 patients and is assessing RP1 in combination with nivolumab in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment. The primary endpoint of this trial is overall survival and key secondary endpoints are progression free survival and overall response rate.
RP2

RP2 in uveal melanoma
The registration-directed REVEAL trial of RP2 in metastatic uveal melanoma is currently enrolling. The clinical trial is expected to enroll approximately 280 patients with metastatic uveal melanoma who are immune checkpoint inhibitor-naïve and evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab. The primary endpoints of the trial are overall survival and progression free survival, and key secondary endpoints are overall response rate and disease control rate.
RP2 in hepatocellular carcinoma (HCC)
The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD1/PD-L1 progressed HCC is currently enrolling. The clinical trial will evaluate RP2 combined with the second-line therapy of atezolizumab and bevacizumab and is expected to enroll 30 patients. The trial is being conducted under a collaboration and supply agreement with Roche.
Upcoming Events

American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting being held May 30-June 3, 2025:
Poster: Response analysis for injected and non-injected lesions and the safety and efficacy of superficial and deep/visceral RP1 injection in the registrational cohort of anti-PD-1 failed melanoma patients of the IGNYTE trial
Poster: Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1
Poster: A randomized, controlled, multicenter, phase 3 study of vusolimogene oderparepvec combined with nivolumab vs. treatment of physician’s choice in patients with advanced melanoma that has progressed on anti-PD-1 and anti-CTLA-4 therapy (IGNYTE-3)
Poster: A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs. ipilimumab plus nivolumab in immune checkpoint inhibitor-naïve patients with metastatic uveal melanoma
Additional poster from an investigator sponsored trial: A phase 1/2 study of vusolimogene oderparepvec (RP1) in primary melanoma (mel) to reduce the risk of sentinel lymph node (SLN) metastasis.
Fireside chat at the Jefferies Global Healthcare Conference on Thursday, June 5, 2025 at 4:20 PM ET
Replimune to host an Investor Day on Tuesday, June 24, 2025 at 10:00 AM ET
Financial Highlights

Cash Position: As of March 31, 2025, cash, cash equivalents and short-term investments were $483.8 million, as compared to $420.7 million as of fiscal year ended March 31, 2024. The increase in cash balance was a result of the public offering in November 2024, somewhat offset by cash utilized in operating activities in advancing the Company’s clinical development plans.

Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of March 31, 2025 will enable the Company to fund operations into the fourth quarter of 2026 which includes scale up for the potential commercialization of RP1 in skin cancers and for working capital and general corporate purposes and excludes any potential revenue.
R&D Expenses: Research and development expenses were $54.0 million for the fiscal fourth quarter and $189.4 million for the fiscal year ended March 31, 2025, as compared to $42.6 million for the fiscal fourth quarter and $175.0 million for the fiscal year ended March 31, 2024. This increase was primarily due to an increase in personnel-related costs as we scaled operations in preparation for commercial launch of RP1, as well as consulting and facility-related costs. Research and development expenses included $4.5 million in stock-based compensation expenses for the fiscal fourth quarter and $18.4 million for the fiscal year ended March 31, 2025.
S,G&A Expenses: Selling, general and administrative expenses were $25.4 million for the fiscal fourth quarter and $72.2 million for the fiscal year ended March 31, 2025, as compared to $16.2 million for the fiscal fourth quarter and $59.8 million for the fiscal year ended March 31, 2024. Selling, general and administrative expenses included $3.8 million in stock-based compensation expenses for the fiscal fourth quarter and $16.6 million for the fiscal year ended March 31, 2025.
Net Loss: Net loss was $74.1 million for the fiscal fourth quarter and $247.3 million for the fiscal year ended March 31, 2025, as compared to a net loss of $55.1 million for the fiscal fourth quarter and $215.8 million for the fiscal ended March 31, 2024.

Conference Call

In connection with this announcement, Replimune will host a conference call and webcast at 8:00 AM ET today. Listeners can register for the webcast via this link. Analysts wishing to participate in the question and answer session should use this link. A replay of the webcast will be available via the Company’s investor website approximately two hours after the call’s conclusion. Those who plan on participating are advised to join 15 minutes prior to the start time.

About RP1

RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2

RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

RWJBarnabas Health and Rutgers Cancer Institute to Present Practice-Changing Research at 2025 ASCO Annual Meeting

On May 22, 2025 Clinicians and scientists from RWJBarnabas Health and Rutgers Cancer Institute reported that it will share new findings and lead discussions at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, showcasing advances from their cutting-edge cancer research program (Press release, Rutgers Cancer Institute of New Jersey, MAY 22, 2025, View Source [SID1234653332]). The meeting will be held in Chicago (and online) from May 30-June 3. Through 45 accepted abstracts and presentations, the institutions will highlight innovative oncology research across a range of tumor types and specialties, including two oral sessions featuring a multisite randomized trial focused on psychosocial support for young adults with cancer, and new findings from a study evaluating pathologic complete response in HER2-positive breast cancer using clinicopathologic variables and the HER2DX pCR score.

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"As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute and RWJBarnabas Health are advancing cancer care through the work of our world-class team of researchers and clinicians, whose groundbreaking studies and collaborative innovation continue to shape the future of oncology," said Steven K. Libutti, MD, FACS, William N. Hait Director, Rutgers Cancer Institute and Senior Vice President, Oncology Services, RWJBarnabas Health. "Our presence at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting underscores our unwavering commitment to confronting cancer on every front, from prevention and early detection to the development of novel therapies that improve outcomes for patients. With the recent opening of the Jack & Sheryl Morris Cancer Center, New Jersey’s first freestanding cancer hospital, we’re excited to mark a new chapter in our mission to transform cancer care and research, expanding our ability to deliver cutting-edge treatments and patient-centric care throughout the region and beyond."

The research accepted for presentation at ASCO (Free ASCO Whitepaper) includes four oral sessions, in addition to numerous poster sessions and publication-only abstracts, all highlighting data across a range of cancers, including breast, colorectal and gastrointestinal.

Highlights of the accepted abstracts include the following:

Results from a multisite randomized trial of Bright IDEAS-Young Adults, a problem-solving skills training intervention, showed statistically and clinically significant improvements in depression, anxiety, and health-related quality of life compared to enhanced usual care among young adults newly diagnosed with cancer. Improvements were attributed to increased problem-solving ability, particularly in reducing the tendency to view problems as significant threats and doubt one’s ability to successfully solve problems.
A national analysis, which found that living in a food desert, clinical trial desert, or area with high transportation vulnerability was independently associated with significantly lower odds of breast cancer clinical trial participation. Patients living in both a food and clinical trial desert had a 27% decreased likelihood of enrollment, highlighting the compounded impact of geographic and socioeconomic barriers such as neighborhood transportation barriers, clinical trial deserts, and food deserts.
Secondary results from the EA1181/CompassHER2 pCR trial, which showed that neoadjuvant THP led to pathologic complete response (pCR) in 64% of HER2+/ER- and 32% of HER2+/ER+ breast cancers. The HER2DX pCR score significantly predicted pCR regardless of ER status, and lower ER expression and higher grade were associated with higher pCR rates.
A single center study evaluated whether requiring tumor biopsies (Bx) in phase I cancer trials affects patient enrollment and participation. Of the 146 patients enrolled across 25 trials, 42.4% underwent at least one study-specific biopsy, most commonly of the liver and lung. Patients who had a biopsy experienced a statistically significant delay—median of 6 days—in initiating treatment and had a shorter average duration on study. Findings suggest that further review is needed to understand factors contributing to shorter study duration among patients who underwent trial-related biopsies.
A review of 283 patients with metastatic colorectal cancer (mCRC) enrolled in phase I trials across two institutions found an overall survival of 8.6 months and a clinical benefit rate of 38.1%, comparable to standard third-line therapies. No significant differences in outcomes were observed across racial or ethnic groups. Most patients had multiple sites of metastases and had received a median of three prior therapies. A non-significant trend suggested that overall survival decreased as the number of prior therapies increased.
A large analysis of over 13,000 patients with cancer of unknown primary (CUP) found that 29% had potentially targetable genetic alterations identified through liquid biopsy. Common mutations included TP53, KRAS, PIK3CA and EGFR. This study is the first to show that liquid biopsy can identify targetable mutations in nearly 30% of CUP patients at a scale comparable to tissue testing. While these findings support its use, further trials are needed to confirm the effectiveness of matched therapies.
The full list of presentations at this year’s 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting can be found here.

City of Hope Researchers to Present Cancer Advances That Could Boost Survival at the American Society of Clinical Oncology (ASCO) Annual Meeting

On May 22, 2025 Researchers from City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center named Top 5 "Best Hospital" in the nation for cancer care by U.S. News & World Report, reported that it will present novel cancer treatment approaches and combinations, leading-edge targeted therapies, and supportive care interventions that could reduce cancer risk and improve survival at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 30 to June 3 in Chicago and online (Press release, City of Hope, MAY 22, 2025, View Source [SID1234653348]).

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This year’s ASCO (Free ASCO Whitepaper) meeting unites nearly 45,000 oncology professionals to discuss leading-edge scientific data and attend educational sessions, empowering health care teams to deliver more personalized and effective lifesaving cancer care to patients.

Highlights of City of Hope’s ASCO (Free ASCO Whitepaper) data include the below, which focus on breast, genitourinary and gastrointestinal cancers.

1015: Real-world data show it is safe to readminister trastuzumab-deruxtecan to metastatic breast cancer patients who experience low-grade lung complications
Attend: Friday, May 30 at 2:57 p.m. CDT in Hall D2

A large, multicenter retrospective study further supports the safety of readministering the antibody-drug conjugate trastuzumab-deruxtecan (T-DXd) to metastatic breast cancer patients after initial drug pauses due to low-grade interstitial lung disease (ILD), which is defined as radiographic evidence of lung inflammation without associated symptoms.

T-DXd is approved for HER2+ and HER2-low and ultra-low advanced breast cancer as well as for many other solid tumors. It carries a rare but serious risk of ILD, requiring frequent imaging and symptom evaluation. Guidelines recommend permanent discontinuation for grade 2 (symptomatic) or higher ILD, but physicians can choose to readminister T-DXd to patients with asymptomatic grade 1 ILD after resolution of imaging findings.

This real-world data of 712 metastatic breast cancer patients treated with T-DXd is significant because limited data exists on the outcomes of readministering T-DXd or "rechallenge" after ILD. The only other dataset included a pooled analysis of nine clinical trials and was presented by Hope S. Rugo, M.D., F.A.S.C.O., City of Hope Women’s Cancers Program director; professor, Department of Medical Oncology & Therapeutics Research, at the 2024 ESMO (Free ESMO Whitepaper) Breast Cancer Annual Congress. This pooled data was recently submitted for publication.

"The real-world data shows that patients with metastatic breast cancer who were treated with trastuzumab-deruxtecan experienced prolonged clinical benefit even if it had to be discontinued temporarily due to low-grade interstitial lung disease. Importantly, patients treated with steroids had faster radiographic ILD improvement, highlighting the importance of early steroid use," said, Dr. Rugo, corresponding author of the ASCO (Free ASCO Whitepaper) abstract.

The researchers collected patient demographics, T-DXd and steroid dosing, imaging results, and outcomes after rechallenge. About 9% of the study’s patients experienced ILD at some level. Some 47 patients were rechallenged — 81% after grade 1 ILD. Among the patients with grade 1 ILD, 56% received steroids for a median of 36 days. Radiographic improvement was seen at a median of 24 days for patients treated with steroids vs. 82 days for those who did not receive steroids.

Among patients rechallenged after grade 1 ILD, recurrent ILD rates were low, with the majority being grade 1. None were grade 5. After rechallenge, patients remained on T-DXd for a median of 215 days. About 26% developed recurrent ILD at a median of 211 days from rechallenge.

4510: Tracking the genomic evolution of kidney cancer and recurrence to identify biomarkers of care
Attend: Saturday, May 31 at 4:54 p.m. CDT in the Arie Crown Theater

Some 20% of renal cell carcinoma (RCC) patients who undergo curative kidney cancer surgery experience disease recurrence. Experts have evaluated in a Phase 3 trial (IMmotion010) whether administering monoclonal antibody atezolizumab post-surgery could prevent RCC from returning and found that it did not.

However, a precision medicine study led by City of Hope’s Sumanta Kumar Pal, M.D., F.A.S.C.O., found that patients who had specific genomic biomarkers in that Phase 3 trial experienced longer disease-free survival when atezolizumab was used after kidney resection.

"We continue to investigate the genetics of kidney cancer patients to understand how we can use this information to prolong life. This study builds on a biomarker, KIM-1, that can identify RCC patients who benefit from adjuvant atezolizumab by using tumor-based genomic features," said Dr. Pal, City of Hope professor, Department of Medical Oncology & Therapeutics.

In the study, the researchers obtained pretreatment tumor tissue samples from 754 patients. Qualifying patient samples were categorized into seven molecular subgroups and further split as biomarker KIM-1 high or KIM-1 low. The scientists found that patients in cluster 6 (stromal/proliferative) appeared to benefit from atezolizumab (n=50). Additionally, patients with KIM-1-high biomarkers and more Teff cells responsible for facilitating immune responses were linked to longer disease-free survival when adjuvant atezolizumab was administered.

"KIM-1 is the most robust predictor of outcome with atezolizumab. We performed whole transcriptome sequencing of RCC tumors before using atezolizumab as well as at disease recurrence, when able, and spotlighted a genomic evolution in disease progression that offers insights into why patients with RCC relapse. Further defining these biomarkers will allow oncologists to provide more personalized care to kidney cancer patients," said Dr. Pal, who is a paid consultant to Roche, the manufacturer of atezolizumab.

3553: A combination treatment of checkpoint inhibitors Vilastobart and atezolizumab shows promise in patients with advanced colorectal cancer
Visit: Saturday, May 31, from 9 a.m. to noon CDT in Hall A

In Phase 2 of a safety and tolerability clinical trial, metastatic colorectal cancer patients who have microsatellite stability (MSS) demonstrated initial evidence of anti-tumor activity when treated with the checkpoint inhibitors Vilastobart (XTX101) and atezolizumab. About 96% of metastatic colorectal cancer cases are MSS.

"This finding is noteworthy because we are seeing a novel combination therapy shrink tumors in a patient population with advanced solid tumors that historically have been nonresponsive to immune checkpoint inhibitors," said Marwan Fakih, M.D., City of Hope professor, Department of Medical Oncology & Therapeutics Research, and lead author of the abstract.

As of this January, 40 patients with MSS colorectal cancer were dosed in Phase 2 of the trial. About 70% of patients had had three or more prior lines of therapy. Those who were previously treated with a type of immune checkpoint inhibitor were excluded.

On the Phase 2 trial, 27% of patients without liver metastatic disease experienced a partial response, defined as more than 50% shrinkage of target lesions. Patients with tumor shrinkage had a significant decrease in circulating tumor DNA, further confirming the clinical efficacy of this combination. The combination was safe as it was associated with a low rate of severe immune-related complications. The safety was further demonstrated by a very low rate of treatment discontinuation.

Vilastobart is an investigational checkpoint inhibitor being developed by Xilio Therapeutics, a company licensing City of Hope technology and co-founded by City of Hope’s Dr. John Williams. Dr. Fakih is a paid advisory board member of Xilio Therapeutics.

5041: Using real-world data to provide insights into treatment that has a lower chance of causing heart attack and stroke in prostate cancer patients
Visit: Monday, June 2, from 9 a.m. to noon CDT in Hall A

A study led by City of Hope’s Alan H. Bryce, M.D., provides decision-making insights to aid with the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), especially those at high risk of cardiovascular events like heart failure and stroke.

The study used real-world data to confirm clinical trial findings which suggest mCRPC patients who have never had chemotherapy and were treated with testosterone blocker abiraterone acetate have a higher risk of hospitalization due to cardiovascular events than patients treated with androgen receptor inhibitor enzalutamide.

Dr. Bryce led a group of scientists who analyzed the data of more than 68 million seniors who are U.S. Medicare and Medicaid beneficiaries. They included mCRPC patients who were 65 or older and have never had chemotherapy. Patients were then stratified into subgroups based on cardiovascular disease history.

People treated with abiraterone acetate had a statistically significant higher risk of experiencing cardiovascular events like heart attacks, strokes, coronary revascularization to restore blood flow, heart failure, irregular heart rhythm and blood clots compared to mCRPC patients treated with enzalutamide. Additionally, the researchers found that the risk of death was higher with abiraterone acetate than with enzalutamide regardless of cardiovascular disease history.

"Real-world data studies like this one are crucial because they provide a broader, more representative perspective on health and disease compared to data from clinical trials, which usually are conducted in controlled settings. Large data sets allow for deeper understanding of how treatments affect patients in real-life scenarios and includes factors not captured in carefully designed clinical trials," said Dr. Bryce, who is a paid speaker for Pfizer, the manufacturer of enzalutamide.

Exelixis Announces Encouraging Results from Phase 1b/2 STELLAR-002 Trial Evaluating Zanzalintinib in Combination with Immune Checkpoint Inhibitors in Advanced Kidney Cancer at ASCO 2025

On May 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported results from an expansion cohort of the phase 1b/2 STELLAR-002 trial evaluating zanzalintinib in combination with either nivolumab (Opdivo) or a fixed-dose combination of nivolumab and relatlimab (Opdualag) in patients with previously untreated advanced clear cell renal cell carcinoma (RCC) (Press release, Exelixis, MAY 22, 2025, View Source [SID1234653302]). These findings, as well as data from multiple dose-escalation cohorts from STELLAR-002, will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"We are pleased to present these preliminary findings from the phase 1b/2 STELLAR-002 study, including early signs of promising activity for zanzalintinib in combination with immune checkpoint inhibitors," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "Data emerging from this ongoing study are important to help inform further evaluation of zanzalintinib-based regimens in advanced solid tumors, including renal cell carcinoma."

Abstract 4515: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Previously Untreated Clear Cell Renal Cell Carcinoma: Results from an Expansion Cohort of the Phase 1b STELLAR-002 Study
Lead Author: Jad Chahoud, M.D., M.P.H., Moffitt Cancer Center, Tampa, Fla., USA
Session Title: Genitourinary Cancer—Kidney and Bladder
Saturday, May 31, 1:15-2:45 p.m. CDT

This expansion cohort of STELLAR-002 included patients with advanced clear cell RCC who received zanzalintinib in combination with either nivolumab (n=40) or fixed-dose nivolumab and relatlimab (n=40) in two non-randomized treatment arms. Patients had unresectable advanced or metastatic disease for which they received no prior systemic therapy. Intermediate- or poor-risk disease, per the International Metastatic RCC Database Consortium, accounted for 75% of patients receiving zanzalintinib in combination with nivolumab and 70% of patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab.

At a median follow-up of 20.1 months for those receiving zanzalintinib in combination with nivolumab and 15.9 months for those receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab, the objective response rates were 63% (95% confidence interval [CI]: 46-77%) and 40% (95% CI: 25-57%), respectively. Disease control rates were 90% (95% CI: 76-97%) for both arms. The 12-month duration of response was 73.4% (95% CI: 50.0-87.1%) and 74.1% (95% CI: 39.1-90.9%), respectively. Median progression-free survival was 18.5 months (95% CI: 9.5 months-not estimable [NE]) and 13.0 months (95% CI: 7.4 months-NE), respectively.

"While significant progress has been made in advanced clear cell renal cell carcinoma, many patients still experience disease progression, and more effective therapies earlier in the treatment landscape are needed," said Jad Chahoud, M.D., M.P.H., Associate Member, Department of Genitourinary Oncology and Medical Director of the Inpatient/Outpatient (IPOP) service at Moffitt Cancer Center in Tampa, Fla., who is presenting the findings. "The high rate of durable responses and long progression-free survival observed for zanzalintinib in combination with nivolumab are encouraging and support further evaluation of this regimen."

Treatment-emergent adverse events (TEAEs) of any grade were reported in all patients. Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with nivolumab included hypertension (n=13), diarrhea (n=6), aspartate aminotransferase increase (n=5), alanine aminotransferase increase (n=5) and palmar-plantar erythrodysesthesia (n=4). Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab included hypertension (n=6), rash (n=6), lipase increase (n=4) and pulmonary embolism (n=4). There were two grade 5 TEAEs in each arm; none were considered related to study treatment. Three patients (8%) in the zanzalintinib in combination with nivolumab arm and eight patients (20%) in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab arm discontinued all study drugs for treatment-related AEs as assessed by investigator.

Abstract 3101: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Advanced Solid Tumors: Results from Two Dose-Escalation Cohorts of the Phase 1b STELLAR 002 Study
Lead Author: Benjamin Garmezy, M.D., Sarah Cannon Research Institute, Nashville, Tenn., USA
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Monday, June 2, 1:30-4:30 p.m. CDT

This analysis of STELLAR-002 included multiple cohorts of patients with advanced solid tumors who received zanzalintinib 100 mg in combination with nivolumab (n=19); zanzalintinib 60 mg in combination with fixed-dose nivolumab and relatlimab (n=24); or zanzalintinib 100 mg in combination with fixed-dose nivolumab and relatlimab (n=25). The most common cancer types for those receiving zanzalintinib in combination with nivolumab were colorectal and prostate cancers, followed by lung cancer and RCC. The most common tumor types in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab cohorts were RCC, followed by prostate cancer, melanoma and colorectal cancer.

The findings showed that the toxicity profile of these combinations was manageable and consistent with each monotherapy agent. Preliminary safety, efficacy and pharmacokinetic results supported selection of the 100 mg dose for zanzalintinib for the ongoing expansion cohorts.

About STELLAR-002
STELLAR-002 (NCT05176483) is a global, open-label phase 1b/2 study of zanzalintinib as a single agent or in combination with nivolumab, fixed-dose nivolumab and relatlimab or nivolumab and ipilimumab in advanced solid tumors. The objective of the study is to evaluate the safety, tolerability and efficacy of zanzalintinib alone and in these combinations. The trial is divided into two parts: a dose-escalation stage and an expansion cohort stage. Expansion cohorts include patients with clear cell RCC, non-clear cell RCC, castration-resistant prostate cancer, urothelial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, colorectal cancer and head and neck squamous cell carcinoma. Exelixis is sponsoring STELLAR-002, and Bristol Myers Squibb is providing nivolumab, ipilimumab and a fixed-dose combination of nivolumab and relatlimab for use in the trial. More information about the trial is available at ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including neuroendocrine tumors, genitourinary, colorectal and head and neck cancers.

About RCC
Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Nearly 81,000 Americans will be diagnosed with kidney cancer in 2025.1 Clear cell RCC is the most common type of kidney cancer in adults.2 Non-clear cell RCC represents about 25% of RCC cases, with fewer treatment options available and poorer outcomes compared with clear cell RCC.3 Advanced or metastatic RCC occurs when the cancer has spread beyond the kidney.4 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%.5 In 2025, approximately 33,700 patients with advanced kidney cancer will require systemic therapy in the U.S., with over 21,400 patients receiving first-line treatment.