On June 1, 2025 Bicara Therapeutics Inc. (Nasdaq: BCAX), a clinical-stage biopharmaceutical company committed to bringing transformative bifunctional therapies to patients with solid tumors, reported updated data from the company’s Phase 1/1b clinical trial of ficerafusp alfa in combination with pembrolizumab in patients with first line (1L) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Bicara Therapeutics, JUN 1, 2025, View Source [SID1234653544]). Ficerafusp alfa is a first-in-class bifunctional antibody designed to enhance tumor penetration by breaking barriers in the tumor microenvironment that have challenged the treatment of multiple solid tumor cancers. Specifically, ficerafusp alfa combines two clinically validated targets: an epidermal growth factor receptor (EGFR) directed monoclonal antibody with a domain that binds to human transforming growth factor beta (TGF-β).

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"Ficerafusp alfa was specifically designed to impact the tumor stroma and drive tumor penetration with the goal of leading to deeper and more durable responses. We’ve now begun to see this translate clinically, with responses lasting nearly two years and contributing to prolonged overall survival in HPV-negative patients, a population that typically faces poor outcomes due to resistance to available therapies," said David Raben, MD, Chief Medical Officer of Bicara Therapeutics. "The strength of the totality of this updated dataset, including 80% of responders achieving a deep response of at least 80% tumor shrinkage, median duration of response of 21.7 months, median progression free survival of 9.9 months, overall survival of 21.3 months, and a 2-year overall survival rate of 46%, provides compelling support for the continued advancement of FORTIFI-HN01, our pivotal Phase 2/3 trial in the first-line recurrent/metastatic setting."

Key highlights from the presentation include:

In the Phase 1/1b trial, ficerafusp alfa in combination with pembrolizumab resulted in deep and durable anti-tumor activity with improved overall survival (OS) compared to historical benchmarks in patients with 1L R/M human papillomavirus (HPV)-negative HNSCC with a PD-L1 combined positive score (CPS) of ≥1 and with at least 24 months of follow-up.
In the efficacy evaluable human papillomavirus (HPV)-negative population (n=28):
Median duration of response (DOR) of 21.7 months amongst responders (n=15).
Median OS of 21.3 months; 2-year OS rate of 46%.
54% (15/28) confirmed objective response rate (ORR); 64% (18/28) ORR, including an additional three unconfirmed responses.
21% (6/28) complete response rate.
80% (12/15) of responders achieved a deep response (≥80% tumor shrinkage).
Disease control rate of 89% (25/28 patients).
Median progression-free survival of 9.9 months.
Manageable safety profile consistent with previously reported adverse events.
"These latest Phase 1/1b data are impressive, particularly the duration of response, which represents a significant advance over historical controls in patients with HPV-negative recurrent/metastatic head and neck squamous cell carcinoma, including anti-PD-1 combinations with chemotherapy or EGFR inhibitors," said Christine H. Chung, MD, Chair of the Department of Head and Neck-Endocrine Oncology and Deputy Physician-in-Chief at the Moffitt Cancer Center. "This reflects the enhanced ability of ficerafusp alfa to remodel the tumor microenvironment allowing the tumor penetration of immune cells required for deep and durable responses in these patients. In addition, the prolonged overall survival, highlighted by a median OS of 21.3 months, reinforces the potential of ficerafusp alfa to address a critical unmet need by delivering durable anti-tumor responses and meaningful improvements in patients’ quality of life."

Conference Call and Webcast Information
Bicara Therapeutics will host a conference call and webcast today, June 1, 2025 at 3:00 p.m. CT / 4:00 p.m. ET. Individuals may register for the conference call by clicking the link here. Once registered, participants will receive dial-in details and a unique PIN which will allow them to access the call. An audio webcast will be accessible through the Investor Relations section of Bicara’s website under Events and Presentations. Following the live webcast, an archived replay will also be available.

About Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosal epithelium in the oral cavity, pharynx and larynx and are the most common malignancies that arise in the head and neck. HNSCC is one of the most common cancers in the United States and globally with a rising incidence anticipated to reach one million new global cases annually by 2030. Ten percent of HNSCC patients are diagnosed with metastatic disease and up to 30% develop a recurrence or metastases over time after receiving initial treatment for advanced HNSCC.

Most cases of HNSCC are thought to result from accumulated mutations caused by carcinogenic exposures such as tobacco smoke or HPV infection. Approximately 80% of patients with R/M HNSCC are HPV-negative. These HPV-negative tumors often exhibit a recurrence pattern that is primarily local and are associated with severe morbidities, including fatal tumor bleeding, intense pain, difficulty swallowing, significant weight loss, and cachexia. This highlights a critical unmet need for therapies that have the potential to deliver durable anti-tumor responses, ultimately leading to meaningful improvements in patients’ quality of life.

About Ficerafusp Alfa
Ficerafusp alfa is a first-in-class bifunctional antibody designed to drive tumor penetration by breaking barriers in the tumor microenvironment that have challenged the treatment of multiple solid tumor cancers. Specifically, ficerafusp alfa combines two clinically validated targets: an epidermal growth factor receptor (EGFR) directed monoclonal antibody with a domain that binds to human transforming growth factor beta (TGF-β). Through this targeted mechanism, ficerafusp alfa reverses the fibrotic and immune-excluded tumor microenvironment driven by TGF-β signaling to enable tumor penetration that drives deep and durable responses.

Ficerafusp alfa is currently being evaluated in FORTIFI-HN01, a pivotal Phase 2/3 clinical trial in patients with first line (1L) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

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.

On May 31, 2025 Xilio therapeutics presented its corporate presentation (Presentation, Xilio Therapeutics, MAY 31, 2025, View Source [SID1234653628]).

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On May 31, 2025 Novocure (NASDAQ: NVCR) reported that results from the Phase 3 PANOVA-3 trial of Tumor Treating Fields (TTFields) therapy for pancreatic cancer will be presented today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago and simultaneously published in the Journal of Clinical Oncology (Press release, NovoCure, MAY 31, 2025, View Source [SID1234653577]).

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"The data presented today from the PANOVA-3 trial of Tumor Treating Fields show a clinically meaningful and statistically significant improvement in overall survival for people with locally advanced pancreatic cancer," said Vincent Picozzi, MD, MMM, medical oncologist and investigator in the PANOVA-3 trial. "Importantly, we also saw an extension in the duration of time before pain progressed. Pain is a hallmark of this disease, and as a clinician, the potential of this therapy to address this aspect of pancreatic cancer is very encouraging. These results illustrate the potential of Tumor Treating Fields therapy concomitant with gemcitabine and nab-paclitaxel to become a standard of care for unresectable, locally advanced pancreatic cancer."

The Phase 3 PANOVA-3 trial evaluated the use of TTFields therapy concomitantly with gemcitabine and nab-paclitaxel as a first-line treatment for unresectable, locally advanced pancreatic adenocarcinoma compared to gemcitabine and nab-paclitaxel alone. The trial met its primary endpoint, demonstrating a statistically significant improvement in median overall survival (mOS) for patients treated with TTFields.

"Most people with pancreatic cancer are diagnosed with advanced disease, which is very difficult to treat and only about 1 in 10 people are alive five years after diagnosis," said Nicolas Leupin, MD, PhD, Chief Medical Officer, Novocure. "The results shared today at ASCO (Free ASCO Whitepaper) and in the Journal of Clinical Oncology demonstrate that Tumor Treating Fields therapy improved overall survival and pain-free survival in unresectable, locally advanced pancreatic cancer. We plan to submit these data to the FDA in the second half of 2025 to support a premarket approval for Tumor Treating Fields therapy."

Results from PANOVA-3

In the intent-to-treat population, patients treated with TTFields therapy concomitantly with gemcitabine and nab-paclitaxel had an mOS of 16.2 months compared to 14.2 months for patients treated with gemcitabine and nab-paclitaxel alone, a statistically significant 2.0-month improvement [hazard ratio (HR) 0.82; p=0.039 (N=571)].

TTFields therapy concomitant with gemcitabine and nab-paclitaxel demonstrated improvement in several secondary endpoints including the one-year survival rate and pain-free survival. Pancreatic cancer can cause significant pain as the disease progresses and managing pain is a key clinical challenge.

The one-year survival rate showed a statistically significant improvement in the TTFields concomitant with gemcitabine and nab-paclitaxel treated group with 68.1% [95% CI: 62.0–73.5] compared to those who received gemcitabine and nab-paclitaxel alone, 60.2% [95% CI: 54.2–65.7], p=0.029.
Patients treated with TTFields concomitant with gemcitabine and nab-paclitaxel had a median pain-free survival of 15.2 months [95% CI: 10.3–22.8] compared to a median 9.1 months in the group treated with gemcitabine and nab-paclitaxel alone [95% CI: 7.4–12.7]; HR 0.74 [95% CI: 0.56–0.97], p=0.027. This is a statistically significant 6.1-month extension in pain-free survival. Pain-free survival was defined as the time from baseline until an increase of 20 or more points was reported by patients on a visual scale for pain or until death.
Quality of life was also measured as a secondary endpoint. Analyses were performed for all patients using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) with the pancreatic cancer specific PAN26 addendum. Deterioration-free survival in global health status, pain and digestive problems were significantly improved in patients receiving TTFields therapy concomitant with gemcitabine and nab-paclitaxel compared to the gemcitabine and nab-paclitaxel alone group. Full analysis of the quality of life results in PANOVA-3 will be shared at a future scientific conference.

There was no statistically significant difference in additional secondary outcome measures of progression-free survival, local progression-free survival, objective response rate, puncture-free survival or tumor resectability rate between the TTFields with gemcitabine and nab-paclitaxel and the gemcitabine and nab-paclitaxel arms.

TTFields therapy was well-tolerated, no new safety signals were observed, and safety was consistent with prior clinical studies. Mild to moderate skin adverse events (AEs) were the most common device-related AEs.

Data Presentation & Publication Details

The PANOVA-3 data, (LBA 3500) Phase 3 study of Tumor Treating Fields (TTFields) with gemcitabine and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma (LA-PAC), will be presented today by Dr. Picozzi in Hall D1 during the 3:00 – 6:00 p.m. Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary oral session.

The Phase 3 PANOVA-3 publication in the Journal of Clinical Oncology, Tumor Treating Fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase 3 PANOVA-3 study, will be available online at View Source

Novocure Investor Event

Novocure will host an investor event featuring Dr. Picozzi and Novocure leadership after the oral presentation. Event details and a link to a live webcast of the event are available on the investor relations page of www.novocure.com. For more information or to request in-person attendance, please contact Novocure investor relations at [email protected].

Regulatory & Ongoing Clinical Study of TTFields for Pancreatic Cancer

Novocure plans to file for regulatory approval for use of TTFields therapy in unresectable, locally advanced pancreatic adenocarcinoma based on PANOVA-3 in the U.S. in the second half of 2025. The company also plans to file for regulatory approval in EU, Japan and other key markets.

Novocure continues to follow patients in its Phase 2 PANOVA-4 trial exploring the use of TTFields therapy together with atezolizumab, gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. PANOVA-4 has completed enrollment with data anticipated in the first half of 2026.

About PANOVA-3

PANOVA-3 is an international, prospective, randomized, open-label, controlled Phase 3 clinical trial designed to test the efficacy and safety of Tumor Treating Fields (TTFields) therapy used concomitantly with gemcitabine and nab-paclitaxel, as a first-line treatment for locally advanced pancreatic adenocarcinoma. Patients were randomized to receive either TTFields therapy concomitant with gemcitabine and nab-paclitaxel or gemcitabine and nab-paclitaxel alone.

The primary endpoint is overall survival. Secondary endpoints include progression-free survival, local progression-free survival, objective response rate, one-year survival rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity.

The PANOVA-3 trial enrolled 571 patients who were randomized 1:1 and followed for a minimum of 18 months.

About PANOVA-4

PANOVA-4 is an international, multi-center, Phase 2 clinical trial designed to test the safety and efficacy of Tumor Treating Fields (TTFields) therapy together with atezolizumab, gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. The primary endpoint is disease control rate. Secondary endpoints include overall survival, progression-free survival, one-year survival rate, objective response rate, progression-free survival at six months, duration of response, and toxicity. The study is designed to enroll 76 patients and enrollment is complete.

About Pancreatic Cancer

Pancreatic cancer is one of the most lethal cancers and is the third most frequent cause of death from cancer in the U.S.i While overall cancer incidence and death rates are remaining stable or declining, the incidence and death rates for pancreatic cancer are increasing.ii It is estimated that approximately 67,000 patients are diagnosed with pancreatic cancer each year in the U.S.iii Pancreatic cancer has a five-year relative survival rate of just 13%.iv

Physicians use different combinations of surgery, radiation and pharmacological therapies to treat pancreatic cancer, depending on the stage of the disease. For patients with locally advanced pancreatic cancer involving encasement of arteries but no extra-pancreatic disease, the standard of care is surgery followed by chemotherapy with or without radiation. Unfortunately, most locally advanced cases are diagnosed when the cancer is no longer operable, generally leaving chemotherapy with or without radiation as the only treatment option.

About Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. These multiple, distinct mechanisms work together to target and kill cancer cells. Due to these multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors.

To learn more about TTFields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On May 31, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive final results from the overall survival (OS) analysis of the Phase III INAVO120 study. These data showed ItovebiTM (inavolisib), in combination with palbociclib (Ibrance) and fulvestrant, reduced the risk of death by more than 30% compared with palbociclib and fulvestrant alone (Press release, Genentech, MAY 31, 2025, View Source [SID1234653576]). This represents a statistically significant and clinically meaningful improvement in overall survival for people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The results are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).

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"For the first time, a PI3K pathway-targeted drug has shown it can help people with this breast cancer subtype live longer," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "Itovebi exemplifies our continued commitment to improve survival rates for people with this common PIK3CA mutation, for whom more effective treatment options are needed."

"The landmark data for the inavolisib-based regimen showed not only a doubling in progression-free survival, but importantly that it extended lives and gave people more time without chemotherapy," said Professor Nicholas Turner, lead study author and professor of molecular oncology at The Institute of Cancer Research, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, London, United Kingdom. "These results give us confidence that this regimen could become the new standard of care in the first-line setting, having demonstrated a substantial benefit on patient outcomes and quality of life."

The Itovebi-based regimen demonstrated a meaningful OS benefit compared with palbociclib and fulvestrant alone. The median OS was 34.0 months (95% CI: 28.4–44.8) for people in the Itovebi arm, compared with 27.0 months (95% CI: 22.8–38.7) in the palbociclib and fulvestrant arm (stratified hazard ratio [HR]=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). The benefit seen in delaying cancer progression was maintained in the updated analysis, with the Itovebi-based regimen showing a consistent improvement in median progression free survival of 17.2 months versus 7.3 months (stratified HR=0.42, 95% CI: 0.32-0.55) in the comparator arm.

The Itovebi-based regimen also led to a statistically significant improvement in objective response rate (the percentage of patients whose signs of cancer completely disappear or their tumors shrink significantly after treatment) and ad-hoc exploratory analyses showed it substantially delayed time to chemotherapy by approximately two years (stratified HR=0.43; 95% CI: 0.30-0.60). No new safety signals were observed at the time of the final OS analysis, with a low discontinuation due to adverse events supporting good tolerability.

Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored Phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations. We are exploring additional studies in breast cancer and other tumor types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations.

About the INAVO120 study

The INAVO120 study [NCT04191499] is a Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:

in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862).
in combination with dual HER2 blockade versus dual HER2 blockade and optional physician’s choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
in combination with CDK4/6i and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in endocrine-sensitive, PIK3CA-mutated HR-positive/HER2-negative breast cancer (INAVO123; NCT06790693).
About hormone receptor (HR)-positive breast cancer

HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

What is Itovebi?

Itovebi (inavolisib) is a prescription medicine used in combination with the medicines palbociclib and fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) gene, and has spread to nearby tissue or lymph nodes (locally advanced), or to other parts of the body (metastatic), and has come back after hormone (endocrine) therapy.

Your healthcare provider will test your cancer for abnormal PIK3CA genes to make sure that Itovebi is right for you.

It is not known if Itovebi is safe and effective in children.

Important Safety Information

What are the possible side effects of Itovebi?

Itovebi may cause serious side effects, including:

High blood sugar levels (hyperglycemia). High blood sugar is common with Itovebi and may be severe. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with Itovebi. Your blood sugar levels may be monitored more often if you have a history of Type 2 diabetes. Your healthcare provider may also ask you to self-monitor and report your blood sugar levels at home. This will be required more frequently in the first 4 weeks of treatment. If you are not sure how to test your blood sugar levels, talk to your healthcare provider. You should stay well-hydrated during treatment with Itovebi. Tell your healthcare provider right away if you develop symptoms of high blood sugar, including:
difficulty breathing
nausea and vomiting (lasting more than 2 hours)
stomach pain
excessive thirst
dry mouth
more frequent urination than usual or a higher amount of urine than normal
blurred vision
unusually increased appetite
weight loss
fruity-smelling breath
flushed face and dry skin
feeling unusually sleepy or tired
confusion
Mouth sores (stomatitis). Mouth sores are common with Itovebi and may be severe. Tell your healthcare provider if you develop any of the following in your mouth:
pain
swelling
redness
ulcers
Diarrhea is common with Itovebi and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney injury. Tell your healthcare provider right away if you develop diarrhea, stomach-area (abdominal) pain, or see mucus or blood in your stool during treatment with Itovebi. Your healthcare provider may tell you to drink more fluids or take medicines to treat your diarrhea.
Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with Itovebi if you develop certain serious side effects.

The most common side effects and abnormal blood test results of Itovebi when used in combination with palbociclib and fulvestrant include:

decreased white blood cell counts, red blood cell counts, and platelet counts
decreased blood levels of calcium, potassium, sodium, and magnesium
increased creatinine blood levels
tiredness
increased blood levels of the liver enzyme alanine transaminase (ALT)
nausea
rash
loss of appetite
COVID-19 infection
headache
Itovebi may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all the possible side effects of Itovebi. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or View Source You may also report side effects to Genentech at (877) 436-3683.

Before you take Itovebi, tell your healthcare provider about all of your medical conditions, including if you:

have a history of diabetes or high blood sugar
have kidney problems
are pregnant or plan to become pregnant. Itovebi can harm your unborn baby.
Females who are able to become pregnant:

Your healthcare provider will check to see if you are pregnant before you start treatment with Itovebi.
You should use effective non-hormonal birth control (contraception) during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Itovebi.
Males with female partners who are able to become pregnant:

You should use effective birth control (contraception) during treatment with Itovebi and for 1 week after your last dose.
are breastfeeding or plan to breastfeed. It is not known if Itovebi passes into your breastmilk. Do not breastfeed during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with Itovebi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see additional Important Safety Information in the full Itovebi Prescribing Information or visit View Source