On June 1, 2025 InnoCare reported latest data of robust oncology pipelines were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, involving the anti-CCR8 antibody ICP-B05 (CM369), the BCL2 inhibitor mesutoclax (ICP-248) and the pan-TRK inhibitor zurletrectinib (ICP-723) (Press release, InnoCare Pharma, JUN 1, 2025, View Source [SID1234653571]).

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Oral Presentation

Title: Preliminary results from the dose-escalation stage of a phase I trial of an anti-CCR8 antibody in patients with relapsed/refractory cutaneous T-cell lymphoma (R/R CTCL) (Abstract No.: 2514)

The current study is the first and only report on the preliminary efficacy data of anti-CCR8 targeted therapy for CTCL patients. The efficacy of ICP-B05 was supported by the PD effects in both skin lesions and peripheral blood in the depletion of CCR8+ cells. ICP-B05 is safe and well tolerated and its safety profile made it a good candidate for combo therapies for CTCL patients with lymph node and other organ involvement.

As of Jan. 6, 2025, a total of 13 patients with R/R CTCL were treated. There were 12 patients received at least one skin lesion assessment followed the mSWAT. 33.3% of patients achieved PR, and 58.3% of patients were assessed as SD with reduction in skin lesion. The 6-month PFS rate was 82.5%, and the median PFS was 11.4 months.

Among the five patients with CCR8+ levels exceeding 10%, four (80%) achieved PR. PK analysis showed that serum exposure (Cmax and AUC0-14D) increased with dose escalation. PD analysis demonstrated significant depletion of CCR8-expressing cells in CTCL skin lesions.

Poster 1:

Title: Preliminary safety and efficacy data of ICP-248, a novel BCL2 inhibitor, in patients with relapsed or refractory B-cell malignancies (Abstract No.: 7038)

The results of ICP-248 monotherapy suggests a well-tolerated safety profile and an exciting efficacy in BTK failed, heavily treated, relapsed or refractory B-cell malignancies.

As of April 15, 2025, a total of 68 patients were enrolled in the dose escalation and dose expansion study. 17 R/R CLL/SLL and 32 R/R MCL patients were treated with 125 mg of ICP-248, including 10 CLL/SLL and 25 MCL patients were previously treated with BTK inhibitors, and 70.0% of CLL/SLL patients and 100% of MCL patients were resistant to BTK inhibitors.

17 CLL/SLL and 26 MCL patients had at least one response assessment. Among the BTK naïve patients, the ORR for R/R CLL/SLL and R/R MCL patients were both 100%, and the CRR was 14.3% and 71.4% respectively, of which 43% of MCL patients reported undetectable minimal residual disease (uMRD). Among the BTK treated patients, the ORR for R/R CLL/SLL and R/R MCL patients were 100% and 78.9% respectively, and the CRR were 30.0% and 26.3% respectively, of which uMRD was reported in 20% of CLL/SLL and 16% of MCL patients.

The median PFS of R/R MCL patients who had received treatment of BTK inhibitors before was 8.3 months. The PFS was not reached among BTK naïve R/R CLL/SLL and R/R MCL patients and BTK-treated R/R CLL/SLL patients.

Poster 2:

Title: Efficacy, safety and pharmacokinetics (PK) of zurletrectinib, a next-generation pan-TRK inhibitor, in pediatric and adolescent patients with NTRK fusion-positive (NTRK+) solid tumors (Abstract No.: 10048)

The integrated analysis demonstrated that zurletrectinib had significant efficacy and good safety profile in pediatric and adolescent patients with NTRK+ solid tumors. Zurletrectinib also showed the potential to overcome the resistance to first generation TRK inhibitors. These findings support zurletrectinib is a better treatment option for NTRK+ pediatric and adolescent patients.

As of Nov. 23, 2024, 18 patients in total were enrolled, including 8 pediatric patients and 10 adolescent patients. Among the 18 patients, 6 TRK inhibitor treatment-naïve patients with central lab confirmed NTRK+ were efficacy evaluable. The confirmed ORR assessed by IRC was 100%.

All patients achieved partial response (PR) at the first tumor assessment and maintained the remission as of the cutoff date. Median time to response were 1.0 month in adolescent patients and 0.9 month in pediatric patients. It is worth noting that one pediatric patient who progressed on prior first-generation TRK inhibitor achieved complete response after receiving zurletrectinib.

Poster 3:

Title: Updated efficacy and safety of zurlectrectinib in adult patients (pts) with locally advanced or metastatic NTRK fusion-positive (NTRK+) solid tumors (Abstract No.: 3112)

In line with previously reported results, zurletrectinib continued to demonstrate a deep and durable responses in adult patients with NTRK+ advanced solid tumors with or without brain metastasis. Zurletrectinib was also well-tolerated and showed favorable safety profile in adult patients with various tumor types.

As of Nov. 23, 2024, a total of 49 TRK inhibitor naïve adult patients were evaluable for efficacy representing 12 different solid tumor types. Among the efficacy population, the distribution of NTRK1, NTRK2 and NTRK3 fusions was 53.1%, 2.0% and 44.9% respectively.

The confirmed ORR by IRC was 83.7%, with CR of 10.2%. Median duration of response (DOR) and median progression-free survival (PFS) by IRC were not reached. The DOR rate and PFS rate by IRC at 12 months was 92.0% and 90.5% respectively. Two of the three patients who had brain metastasis at the baseline achieved intracerebral ORR, which is consistent with the good brain penetration and strong intracranial activity of zurletrectinib.

The 2025 ASCO (Free ASCO Whitepaper) Annual Meeting is held from May 30 to June 3, 2025 in Chicago, U.S. The ASCO (Free ASCO Whitepaper) annual meeting is the most important and professional academic event in the global oncology field, which showcases the international cutting-edge clinical oncology research results and tumor treatment technologies.

On June 1, 2025 AstraZeneca reported positive results from the MATTERHORN Phase III trial showed perioperative treatment with Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) versus chemotherapy alone (Press release, AstraZeneca, JUN 1, 2025, View Source [SID1234653555]). Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.

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These results will be presented today during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (abstract #LBA5) and simultaneously published in The New England Journal of Medicine.

In a planned interim analysis, patients treated with the Imfinzi-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001). Estimated median EFS was not yet reached for the Imfinzi arm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the Imfinzi-based perioperative regimen were event-free at one year compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively, signaling a greater magnitude of benefit over time for the Imfinzi-based regimen.

For the secondary endpoint of overall survival (OS), a strong trend was observed in favour of the Imfinzi-based perioperative regimen (HR=0.78; 95% CI 0.62-0.97; p=0.025). The trial will continue to follow OS, which will be formally assessed at the final analysis.

Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, and principal investigator for the trial, said: "Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease. Results from the MATTERHORN trial showed that more than two-thirds of patients treated with a durvalumab-based perioperative regimen had not experienced a recurrence or were progression-free after two years. This new treatment approach should become the new standard of care in this setting based on these results."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "This immunotherapy-based perioperative regimen has the potential to change the clinical paradigm in early gastric and gastroesophageal junction cancers based on the reduction in risk of progression, recurrence or death by nearly a third and the strong trend towards improved survival. As the third positive trial of perioperative treatment with Imfinzi across multiple tumour types, the MATTERHORN trial further validates this approach and highlights our commitment to bringing novel therapies to early stages of disease where there is the greatest chance for cure."

Summary of results: MATTERHORN

Imfinzi-based regimen

(n=474)

Chemotherapy regimen

(n=474)

EFSi

Median EFS (95% CI) (in months)

NR (40.7-NR)

32.8 (27.9-NR)

HR (95% CI)

0.71

(0.58-0.86)

p-valueii

p<0.001

EFS rate at 12 months (%)

78.2

74.0

EFS rate at 24 months (%)

67.4

58.5

OS

mOS (in months)

NR

47.2

HR (95% CI)

0.78

(0.62-0.97)

p-valueiii

p=0.025

i. EFS rates are based on Kaplan Meier estimates.

ii. Threshold to declare statistical significance p-value<0.0239.

iii. Threshold to declare statistical significance p-value<0.0001.

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.1 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.1 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.2 In 2024, there were approximately 43,000 drug-treated patients in the US, European Union (EU) and Japan with early-stage and locally advanced gastric or GEJ cancer.3 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.4

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.5

Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy. Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and one in four patients do not survive beyond two years, reflecting high unmet medical need.6-7 Additionally, the five-year survival rate remains poor, with less than half of patients alive at five years.8

MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomization until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centres in 20 countries, including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In addition to its indications in GI cancers, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.

Imfinzi is approved in the US and other countries as a perioperative treatment in combination with neoadjuvant chemotherapy for muscle-invasive bladder cancer based on the NIAGARA Phase III trial. Additionally, Imfinzi plus standard-of-care Bacillus Calmette-Guérin induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial.

Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.

On June 1, 2025 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported the first data for casdatifan plus cabozantinib in an oral presentation by Dr. Toni K. Choueiri, Dana-Farber Cancer Institute, at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Arcus Biosciences, JUN 1, 2025, View Source [SID1234653572]).

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"I was very encouraged to see that nearly half of patients had a confirmed response to the casdatifan plus cabozantinib combination despite short follow-up," said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber, the Jerome and Nancy Kohlberg Chair and professor of medicine at Harvard Medical School, and lead investigator of ARC-20. "Casdatifan plus cabozantinib was well tolerated, and the safety profile was consistent with that of either agent alone, supporting their potential as a combination therapy. I look forward to enrolling patients into the PEAK-1 trial as soon as it is open."

"The initial data for casdatifan plus cabozantinib in the ARC-20 study have already exceeded the historic benchmarks for either agent alone, as well as that of another HIF-2a inhibitor plus cabozantinib in the same second-line setting," said Terry Rosen, Ph.D., chief executive officer of Arcus. "These data serve as the proof of concept for PEAK-1, which will be initiated in the coming weeks and is designed to generate evidence to change the standard of care for people who have progressed on prior immunotherapy treatment."

ARC-20 is a Phase 1/1b dose-escalation and expansion study that includes a cohort evaluating once-daily 100mg of casdatifan plus 60mg of cabozantinib in patients with ccRCC who had progressed on prior immunotherapy. At the time of the data cutoff (DCO, March 14, 2025), 42 participants were evaluable for safety, and 24 reached at least 12 weeks of follow-up and were evaluable for efficacy. Among the safety-evaluable population (N=42), most participants (79%) had an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factor of intermediate or poor. Nearly half (46%) of the efficacy-evaluable population (N=24) achieved a confirmed response per RECIST 1.1, and only one patient had primary progressive disease. The vast majority of the efficacy-evaluable population remains on treatment.

In the safety-evaluable population, no unexpected safety risks were identified at the time of DCO, and casdatifan plus cabozantinib had an acceptable safety profile with no meaningful overlapping toxicity for the two drugs. Only two patients discontinued any drug, and no patients discontinued treatment with both drugs. The incidence of treatment-emergent adverse events (TEAEs) with casdatifan, particularly anemia and hypoxia, was similar to TEAEs observed with casdatifan monotherapy, and there were no casdatifan-related Grade 4 or 5 adverse events. The incidence of TEAEs associated with each drug was consistent with what is expected for each drug alone.

A summary of the efficacy and safety results is below.

Efficacy-Evaluablea

casdatifan 100mg QD + cabozantinib 60mg QD

(n=24)

Median Follow-Up

5.3 months

Confirmed ORR (cORR) per RECIST v1.1 [95% CI]

46% (11)b

[26,67]

Best Overall Response:

Complete Response

4% (1)

Partial Response

42% (10)b

Stable Disease

50% (12)

Progressive Disease

4% (1)

CI: confidence interval; QD: daily

a All eligible patients who received any study treatment and reached a minimum of 12 weeks follow-up or discontinued due to progression or death.

b Inclusive of one patient who had partial response confirmation after March 14, 2025.

Safetya

casdatifan 100mg QD + cabozantinib 60mg QD

(n=42)

casdatifan

cabozantinib

Patients with any Treatment-Related Grade ≥3 AEb

Anemia

24% (10)

14% (6)

Hyponatremia

0

7% (3)

Hypoxia

7% (3)

0

Hypertension

0

5% (2)

Neutrophil count decrease

2% (1)

5% (2)

Patients with any AE leading to dose reductionb

Fatigue

2% (1)

12% (5)

Anemia

10% (4)

2% (1)

Hypoxia

10% (4)

0

Palmar-plantar erythrodysesthesia

0

5% (2)

Stomatitis

0

5% (2)

AE: adverse event

a Safety population included patients who received any amount of study drug and had at least one month of safety follow-up at the data cutoff date.

b Treatment-emergent adverse events (grade 3 or higher) related to casdatifan, cabozantinib, or any study drug reported in ≥3% of patients in any treatment arm.

Arcus is pursuing a broad development program in both the immuno-oncology (IO)-naive and post-IO settings with differentiated combinations to maximize the opportunity for casdatifan in ccRCC. These studies include:

Arcus’s planned Phase 3 study, PEAK-1, which will evaluate casdatifan plus cabozantinib versus cabozantinib monotherapy as a first- or second-line treatment in patients with metastatic ccRCC who have previously received anti-PD-1/PD-L1 therapy. The primary endpoint will be PFS with a key secondary endpoint of overall survival.
eVOLVE-RCC02, a Phase 1b/3 study sponsored by AstraZeneca, which will evaluate casdatifan plus volrustomig, an investigational anti-PD-1/CTLA-4 bispecific antibody, as first-line treatment for participants with ccRCC.
ARC-20, which includes three cohorts evaluating casdatifan in earlier-line settings, including casdatifan plus zimberelimab in first-line ccRCC, casdatifan monotherapy in favorable risk ccRCC, and casdatifan monotherapy in immunotherapy-experienced, TKI-naive settings.
Investors may dial in to the conference call at +1 404 975 4839 (local) or +1 833 470 1428 (toll-free) using Conference ID: 446724 on Monday, June 2, 2025, at 5:00 AM PT / 7:00 AM CT. Participants may also register for the call online using the following link: View Source To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay will be available following the live event.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor responsible for activating multiple tumor growth pathways in hypoxic and pseudo-hypoxic tumor environments. By selectively binding HIF-2a, casdatifan is designed to shut down hypoxic oncogenesis and key oncogenic pathways, which leads to cancer cell death. Clear cell renal cell carcinoma is almost universally associated with HIF-2a dysregulation. Casdatifan is currently being evaluated in ARC-20, a Phase 1/1b study in renal cell carcinoma.

Casdatifan is an investigational molecule. Approval from any regulatory authority for its use has not been received, and its safety and efficacy have not been established.

About RCC

According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 80,980 Americans will be diagnosed with kidney cancer in 2025. Clear cell RCC is the most common type of kidney cancer in adults. 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%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.

On June 1, 2025 Protagonist Therapeutics, Inc. ("Protagonist") (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) reported detailed results from the Phase 3, randomized, placebo-controlled VERIFY study evaluating rusfertide in patients with polycythemia vera (PV), which met the primary and all key secondary endpoints (Press release, Takeda, JUN 1, 2025, View Source [SID1234653573]). The data will be presented as a late-breaking oral presentation at the 61st American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting Plenary Session (LBA3) at 2:09 pm CDT today.

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PV is characterized by overproduction of red blood cells (erythrocytosis), which may increase blood viscosity, or thickness, potentially resulting in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. People with PV can experience burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus, which may negatively impact their daily functioning and quality of life. Hematocrit is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate symptoms, but many patients still experience uncontrolled hematocrit levels with current standard of care treatments.

Rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic, is under evaluation in the Phase 3 VERIFY study for its potential to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV. In the study, patients dependent on frequent phlebotomy, with or without treatment with cytoreductive therapy, were randomized to receive once-weekly rusfertide or placebo, as an add-on to current standard of care treatment.

"PV poses significant challenges for patients, including debilitating symptoms and the risk of serious thrombotic events, and hematocrit control is crucial to improving patient outcomes. The VERIFY study demonstrated that treatment with rusfertide controls hematocrit levels in phlebotomy-dependent patients, including patients receiving cytoreductive therapies," said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "These results suggest rusfertide has the potential to become part of the standard of care treatment for patients with PV."

The study met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during study Weeks 20-32. Study results demonstrated 76.9% of patients treated with rusfertide plus current standard of care achieved a clinical response, compared to 32.9% in the placebo plus current standard of care group (p<0.0001).1 The response observed in the rusfertide arm was consistent across subgroups, regardless of risk status or type of concurrent cytoreductive therapy.1 In addition, all key secondary endpoints met statistical significance in favor of the rusfertide arm compared to the placebo arm in the VERIFY study, as follows:

The mean number of phlebotomies was 0.5 phlebotomies per patient for those treated with rusfertide plus current standard of care compared to 1.8 phlebotomies per patient for those treated with placebo plus current standard of care during Weeks 0-32 (p<0.0001).1
Only 27% of patients treated with rusfertide plus current standard of care required phlebotomy between Weeks 0-32, compared to 78% of patients who received placebo plus current standard of care.
The mean number of phlebotomies during Weeks 0-32 in the rusfertide arm was reduced across subgroups, including risk status and use of concurrent cytoreductive therapy, versus the placebo arm.
62.6% of patients treated with rusfertide plus current standard of care maintained hematocrit levels below 45% versus 14.4% treated with placebo plus current standard of care (p<0.0001).1
Rusfertide also showed statistically significant improvements in mean change from baseline to Week 32 in PROMIS Fatigue2 (p<0.03) and the MFSAF Total Symptom Score3 (p<0.03). Rusfertide is the first investigational therapy to prospectively demonstrate a statistically significant improvement in these patient-reported outcomes (PROs) of fatigue and symptom burden in patients with PV.1
Rusfertide was generally well tolerated. The majority of adverse events were low grade and non-serious and no serious adverse events considered related to rusfertide were reported. There was no evidence of increased risk of cancer in patients treated with rusfertide plus current standard of care compared to patients treated with placebo plus current standard of care at the time of the primary analysis. Cancer events were reported in one patient in the rusfertide arm (0.7%) and in seven patients in the placebo arm (4.8%). The most common treatment-emergent adverse events were localized injection site reactions (55.9%), anemia (15.9%) and fatigue (15.2%).1

"These findings underscore rusfertide’s potential as a first-in-class erythrocytosis-specific treatment for PV and validate more than a decade of scientific innovation originating from Protagonist’s peptide technology platform," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "We would like to thank all the patients, study staff and investigators for participating in the VERIFY study. We are pleased to partner with Takeda as we continue to advance rusfertide to potentially transform the standard of care in PV patients around the world."

"These promising pivotal data strongly support rusfertide’s potential benefit for a broad spectrum of patients with PV who may be receiving current standard of care therapies but not achieving adequate hematocrit control," said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit (OTAU) at Takeda. "We look forward to receiving additional data from the VERIFY trial later this year, advancing rusfertide towards regulatory approval and continuing our collaboration with Protagonist to bring this innovative therapy to patients."

Rusfertide has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA).

Takeda Investor Conference Call and Webcast Details

Takeda will host an investor call regarding this update on Sunday, June 1, 6-6:45 pm CDT/ 7-7:45 pm EDT / Monday, June 2, 08:00-08:45 (JST).

The call will be held using the Zoom platform and Zoom simultaneous interpretation function. Kindly pre-register from the below link:
View Source

An on-demand replay will be made available on Takeda’s website after the conclusion of the event.

Protagonist Investor Conference Call and Webcast Details

The dial-in numbers for Protagonist’s investor update on Monday, June 2nd at 5:00-6:00 am PDT/ 8:00-9:00 am EDT are:

US-based Investors: 1-877-300-8521
International Investors: 1-412-317-6026
Conference Call ID: 10199589
The webcast link for the event can be found here: View Source;tp_key=360d3b714d

A replay of the presentation will be available on the Protagonist Investor Relations Events and Presentations webpage following the event.

About VERIFY

The Phase 3 VERIFY study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during Weeks 20-32, which was defined as the absence of "phlebotomy eligibility." To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%.

All patients have completed their participation in the randomized, placebo-controlled portion of the study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study.

On June 1, 2025 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported updated data from the Phase 1 TRAVERSE study of ALLO-316 in renal cell carcinoma (RCC) during an oral presentation at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Allogene, JUN 1, 2025, View Source [SID1234653541]). The Phase 1 TRAVERSE trial enrolled patients with advanced or metastatic renal cell RCC. Leveraging the proprietary Dagger technology to enable robust CAR T cell expansion, it stands as the first and only allogeneic CAR T product to show promise in treating solid tumors. The presentation focused on the Phase 1b expansion cohort from the Phase 1 TRAVERSE study in which patients were treated with a standard regimen of cyclophosphamide and fludarabine followed by a single dose of 80 million AlloCAR T cells.

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"ALLO-316 is showing clear evidence of targeted antitumor activity in patients who had failed most or all approved therapies for advanced or metastatic renal cell carcinoma," said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer at Allogene. "Our proprietary Dagger technology allows the use of a standard cyclophosphamide and fludarabine-based lymphodepletion regimen with a single dose of ALLO-316. Strong CAR T-cell kinetics and extensive infiltration of tumor tissue by CAR T cells are combining to generate deep and durable remissions. These are results that were previously considered out of reach for patients with advanced solid tumors."

"Patients diagnosed with advanced or metastatic renal cell carcinoma often face a median survival in months after exhausting standard therapies," said Samer A. Srour, MB ChB, MS, Associate Professor of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center and lead investigator of the TRAVERSE trial. "These updated results from a larger cohort of patients with confirmed CD70 positive tumors provide compelling evidence that treatment with ALLO-316 can reduce tumor burden, control disease, and in some cases deliver durable responses. These findings underscore the clinical promise of an allogeneic CAR T to address the significant unmet needs in solid tumors and offer hope to patients who have exhausted other options."

In the Phase 1b expansion cohort, 22 patients whose tumors had progressed on multiple prior therapies were treated with lymphodepletion and 20 were treated with ALLO-316. All patients had tumors resistant to immune checkpoint blockers and at least one tyrosine kinase inhibitor (TKI), 82% had ≥2+ prior TKI, and 41% had prior belzutifan. Sixteen of the ALLO-316 treated patients had a high CD70 Tumor Proportion Score (TPS >50%). The Phase 1b expansion cohort evaluated the safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC lymphodepletion regimen (fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/day) for 3 days). The median time from enrollment to the start of therapy was four days.

A single dose of ALLO-316 stabilized or reversed disease progression in the majority of patients. In the 16 patients with CD70 TPS ≥50%, the trial demonstrated a Confirmed Overall Response Rate (ORR) of 31% with 44% achieving a minimum of 30% reduction in tumor burden. Of the five confirmed responders, four maintain ongoing responses, with one in sustained remission for over 12 months. The median duration of response (mDOR) has not yet been reached, indicating the potential for long-term disease control.

CD70+ patients Phase 1b
(N=20)
ORR (confirmed CR or PR per RECIST v1.1), n/N (%)
5/20 (25)
CD70 TPS ≥50%
CD70 TPS <50% 5/16 (31)
0/4 (0)
RECIST v1.1, Response Evaluation Criteria in Solid Tumors, version 1.1; TPS, tumor proportion score

The safety profile of ALLO-316 was manageable and consistent with lymphodepletion and an active CAR T product. The most frequent Grade ≥3 events were hematologic and there were no treatment-related Grade 5 events. The most common all-grade adverse events were cytokine release syndrome (CRS) (68%; with no grade ≥3), neutropenia (68%), decreased white blood cell count (68%), anemia (59%), and thrombocytopenia (55%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was 18% (with no grade ≥3) and no graft-versus-host disease (GvHD) occurred. Improved recognition of IEC-HS symptoms led to diagnosis in 36% of patients with 2 patients (9%) experiencing a short-term Grade 3 (one) or Grade 4 (one patient) event. Newly implemented diagnostic and management algorithms significantly mitigated IEC-HS, with no associated Grade 5 events.

TEAEs ≥20% incidence in Phase
1b, n (%) Phase 1b (N=22a)
All Grades Grade ≥3
Neutropenia 15 (68) 15 (68)
White blood cell count decreased 15 (68) 15 (68)
Anemia 13 (59) 9 (41)
Thrombocytopenia 12 (55) 6 (27)
Nausea 8 (36) 0
ALT increased 7 (32) 2 (9)
Peripheral edema 7 (32) 0
Pyrexia 7 (32) 0
Arthralgia 6 (27) 0
AST increased 6 (27) 2 (9)
Fatigue 5 (23) 0
Headache 5 (23) 0
AEs of Special Interest Any Grade Grade ≥3
CRS 15 (68) 0
Infection 10 (45) 8 (36)
IEC-HS 8 (36) 2 (9)b
ICANS 4 (18) 0
Graft-versus-host disease 0 0

IEC-HS includes the preferred terms immune effector cell-associated HLH-like syndrome and Hemophagocytic lymphohistiocytosis.
a Includes 2 patients who received LD but did not receive ALLO-316
b One patient experienced G4 IEC-HS based on GI bleeding with subsequent improvement and 1 patient experienced G3 IEC-HS based on hypotension managed without pressors with subsequent improvement.

About ALLO-316 (TRAVERSE)
ALLO-316 is an AlloCAR T investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In October 2024 the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation based on the potential of ALLO-316 to address the unmet need for patients with advanced or metastatic RCC. The FDA previously granted Fast Track Designation (FTD) to ALLO-316 in March 2023. In April 2024, the Company announced an award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC.