On June 18, 2024 XBiotech (NASDAQ: XBIT) reported data from its Phase 1/Phase 2 randomized, double-blind, placebo-controlled multi-center study for advanced pancreatic cancer (Press release, XBiotech, JUN 18, 2024, View Source [SID1234644427]). Known as 1-BETTER, the study examined Natrunix (anti-interleukin-1alpha) antibody in combination with an established chemotherapy regimen (ONIVYDE (ON) + 5-Fluorouracil (5FU) + Leucovorin (LV), a regimen that is already widely used for treating pancreatic cancer but is associated with difficult toxicities and less then ideal survival outcomes. Natrunix was being evaluated as an anti-cancer agent for use in cytotoxic chemotherapy combinations where the Company believes it might potentially also improve tolerability of the chemotherapy.

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The Phase 1 portion was a dose escalation study in metastatic pancreatic cancer patients to determine if dose limiting toxicities (DLTs) occurred in combination with the ON+5FU+LV regimen in second- or third-line setting. DLTs were not expected with Natrunix and none were seen. The Natrunix dose in the Phase 2 portion was thus the highest dose used in the Phase 1 portion.

Sixty-five subjects were randomized into the Phase 2 study on a 1:1 basis to receive either Natrunix+ ON+5FU+LV (Arm1) or Placebo +ON+5FU+LV (Arm2). There were 33 subjects enrolled into Arm1 and 32 into Arm2. The Phase 2 treatment period was 24-weeks with subjects receiving therapy once every other week for a total of 12 cycles.

Subjects included in the study had confirmed metastatic, unresectable, or recurrent pancreatic adenocarcinoma of exocrine pancreas and were required to have had disease progression after one prior gemcitabine-based therapy or one FOLFIRINOX and gemcitabine containing therapy. All patients were required to have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1).

The primary endpoint for the Phase 2 study was to assess the safety and tolerability of Natrunix when used with the ON+5FU+LV combination. Overall, there were fewer adverse events (AEs) of any kind during the 24-week treatment period for the Natrunix arm compared to placebo (297 vs 336), with markedly fewer events in specific categories of adverse events during that time. There was a 28% reduction in the number of subjects experiencing significant adverse events (SAEs) in the Natrunix arm (9 out of 33) versus placebo (12 out of 32) that occurred during the 24-week treatment period. Subjects receiving the Natrunix ON+5FU+LV regimen also had about a 33% reduction in hospitalization (80 days versus 120 days) during the 24-week treatment period compared to subjects receiving placebo + ON+5FU+LV combination.

Subjects receiving the Natrunix combination also reported a 22% reduction in fatigue (28 vs 36), 32% improved appetite (19 vs 28) and 41% reduction in pain (17 vs 29) as of the last day of the 24-week treatment period compared to subjects receiving the placebo ON+5FU+LV combination.

Severe diarrhea that can be life -threatening is a significant complication for the ON+5FU+LV regimen. There was a two-fold reduction (9% versus 19%) in the incidence of severe diarrhea during the 24-week treatment regimen for patients receiving the Natrunix + ON+5FU+LV combination compared to placebo + ON+5FU+LV.

Overall Survival (OS), one of the secondary endpoints for the Phase 2 study, was conventionally defined in as time from randomization to death. The sample size for the study included intent-to-treat analysis of 33 subjects randomized into the Natrunix + ON+5FU+LV arm versus 32 subjects in Placebo + ON+5FU+LV arm. A Kaplan-Meier Survival Curve using a product limit comparison method was performed. This data highlights the observation that no subjects in the placebo ON+5FU+LV group (n=32) survived for longer than 330 days, whereas 8 subjects in the Natrunix ON+5FU+LV arm (n=33) were still alive as of day 330. Considering the small sample size, the borderline statistically significant p-value of p = 0.096 suggests prolonged survival for subjects receiving the Natrunix regimen.

The lead investigator for the study, David J. Park, MD Medical Oncologist, Medical Director for the providence St. Jude Crosson Institute, Fullerton, CA stated "Treatment of advanced pancreatic cancer in the second and third line settings presents significant challenges in terms of toxicity as well as efficacy. To observe these trends for reduced toxicity and potential survival benefit is remarkable, particularly given the limited sample size. The potential interaction between reduced toxicity, more time on treatment and improvement in survival makes intuitive sense for clinicians who treat these patients. These findings are extremely important."

While there was a relatively small number of pancreatic cancer patients enrolled in the Phase 2 portion of the study, in the Company’s opinion, the findings show better outcomes for the Natrunix + ON+5FU+LV group as compared to the control arm. The Company believes that the reduced number of serious and adverse events, the significant reduction in hospitalization, and improved OS during the respective time periods described above for each of these metrics suggest that Natrunix could represent a breakthrough advance for the treatment of pancreatic cancer.

On June 18, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported the company plans to report new data from the global randomized Phase 1b/2 combination study of amezalpat (TPST-1120) with atezolizumab and bevacizumab in first-line treatment of hepatocellular carcinoma (HCC) in a premarket press release followed by a webcasted conference call with associated slide presentation on Thursday, June 20, 2024 at 8:30 a.m. ET (Press release, Tempest Therapeutics, JUN 18, 2024, View Source [SID1234644426]).

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To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the investor section of the Tempest website at View Source The webcast will be available for replay for 30 days.

On June 18, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported randomization of the first patient in the PRISM-MEL-301 trial, assessing the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02), in combination with nivolumab, in first-line advanced or metastatic cutaneous melanoma (Press release, Immunocore, JUN 18, 2024, View Source [SID1234644424]).

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"We are very proud to have started the registrational program for brenetafusp, our PRAME candidate, supported by the recent promising brenetafusp monotherapy data in late-line cutaneous melanoma" said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The PRISM-MEL-301 trial – the first Phase 3 trial for any PRAME-targeted therapy – will test whether combining brenetafusp with nivolumab may be a more effective treatment option than current standards of care for newly diagnosed metastatic or advanced cutaneous melanoma patients."

The Phase 3 trial (NCT06112314) will randomize HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country. Bristol Myers Squibb will provide nivolumab.

Professor Georgina Long, Co-Medical Director of Melanoma Institute Australia, said: "The PRISM-MEL-301 Phase 3 trial is a great example of outside-the-box scientific thinking, leveraging the immune system in a new way in the hope of beating cancer. My hope is that we can get closer to our goal of zero deaths from melanoma by conducting clinical trials with innovative drug therapies such as this."

The Company has shared the cutaneous melanoma Phase 1 data during an oral presentation at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on 31 May. The data showed that brenetafusp was well tolerated as monotherapy and in combination with anti-PD1, and demonstrated promising monotherapy clinical activity, including disease control rate (partial response and stable disease), progression free survival, and circulating tumor DNA molecular response.

Brenetafusp is the first PRAME x CD3 ImmTAC bispecific protein targeting an HLA-A*02:01 PRAME (PReferentially expressed Antigen in Melanoma) antigen. The Company is continuing to enroll patients into a Phase 1/2 trial in monotherapy and combination arms across multiple tumor types, including three expansion arms for patients with advanced ovarian, non-small cell lung, and endometrial cancers.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About PRISM-MEL-301 – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial will randomize HLA-A*02:01-positive patients with previously untreated advanced melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the brenetafusp dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Ph1 monotherapy continues in additional solid tumors as well as multiple combinations with standards-of-care, including checkpoint inhibitors, chemotherapy, targeted therapies, and tebentafusp.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.

On June 18, 2024 Precision-Panc team at the University of Glasgow, with their Co-Sponsor, NHS Greater Glasgow & Clyde, reported the opening of the Phase II PRIMUS-006 study evaluating IMM-101, a broad-spectrum immunomodulatory agent containing heat-killed, whole cell Mycobacterium obuense, in combination with gemcitabine and pembrolizumab as first-line treatment in patients with metastatic pancreatic cancer (Press release, Immodulon Therapeutics, JUN 18, 2024, View Source [SID1234644423]). The PRIMUS-006 study is part of the Precision-Panc Platform master protocol program, which is Co-Sponsored by NHS Greater Glasgow & Clyde and the University of Glasgow and co-ordinated by the Glasgow Oncology Clinical Trials Unit. PRIMUS-006 is endorsed by Cancer Research UK (CRUK Reference: A31505).

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The study is funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A., through its investigator-initiated program with provision of study drug and financial support.The study is also funded by Immodulon Therapeutics Ltd through its investigator-initiated program with provision of study drug and financial support for the study.

"The opening of the Phase II PRIMUS-006 study is an important milestone in the pursuit to develop new treatment options to improve the overall outcomes in patients diagnosed with pancreatic cancer," said Professor David Chang, principal investigator and professor of surgical oncology & honorary consultant pancreatic surgeon, Wolfson Wohl Cancer Research Centre, University of Glasgow and Glasgow Royal Infirmary. "The selection of IMM-101 to comprise part of the triplet combination reflects its potential to enhance anti-tumour activity alongside gemcitabine and pembrolizumab in patients with first-line metastatic pancreatic cancer," said Professor Jeff Evans of the University of Glasgow and Honorary Consultant in Medical Oncology at the Beatson West of Scotland Cancer Centre, Glasgow.

Pancreatic ductal adenocarcinoma (PDAC) tends to be poorly immunogenic with diminished antigen presentation and a highly immunosuppressive tumour micro-environment that further impedes the functional activation of cytotoxic T lymphocytes. Based on the ability of gemcitabine to enhance the expression of antigen-presenting molecules, its use in combination with IMM-101, a broad-spectrum immunomodulator with potential to sensitize pancreatic cancers to immune checkpoint inhibition, and pembrolizumab, MSD’s anti-PD-1 therapy, this novel combination has the potential to enhance anti-tumour efficacy in patients with first-line pancreatic cancer.

"This is an exciting opportunity to be part of a high caliber pancreatic cancer research program and reflects the potential of IMM-101 to become a backbone therapy in immunologically cold tumours by enhancing the efficacy of existing anti-cancer treatment options, including chemotherapy and checkpoint inhibitors," said Josefine Roemmler-Zehrer, MD, Associate Professor, and Chief Medical Officer of Immodulon. "We look forward to working with the Co-Sponsors NHS Greater Glasgow & Clyde and University of Glasgow, MSD and other key collaborators to support this study and advance our efforts to bring IMM-101 closer to patients diagnosed with pancreatic cancer and other solid tumours."

The Phase II PRIMUS-006 study is a single-arm clinical study evaluating IMM-101, gemcitabine and pembrolizumab as first-line combination triplet therapy in patients diagnosed with metastatic pancreatic cancer who are deemed not sufficiently fit enough to tolerate treatment consisting of two or more cytotoxic agents. As the overall objective of the study is to enhance the anti-tumour activity of immunotherapy, the primary endpoint of the study is the objective response rate as defined by RECIST 1.1. Key secondary endpoints include safety and tolerability, evaluation of progression-free survival, disease control rate and overall survival. Up to 50 patients with metastatic pancreatic ductal adenocarcinoma will be treated in the study from approximately 15-20 hospital sites in the United Kingdom.

About Pancreatic Ductal Adenocarcinoma (PDAC)

PDAC is the third most common cause of cancer death in the developed world. Approximately 50% of patients present with metastatic disease and most of the patients who present with resectable or locally advanced inoperable disease ultimately develop metastatic disease.

Gemcitabine monotherapy has modest clinical benefit and a marginal survival advantage in patients with metastatic PDAC. Better response rates and survival can be achieved with the FOLFIRINOX regimen, and with the addition of nab-paclitaxel to gemcitabine.

Nevertheless, overall survival remains disappointing with these combination cytotoxic chemotherapy regimens.
Furthermore, many patients are not fit enough to tolerate these combination regimens, and these patients are invariably excluded from participation in clinical trials because of lower performance status. Consequently, these patients represent a significant unmet clinical need and are in urgent need of novel therapeutic approaches.

About IMM-101

IMM-101 is a systemic, broad-spectrum immunomodulator containing heat-killed, whole cell Mycobacterium obuense, capable of generating a broad systemic innate and adaptive type 1 immune response with potential to treat immunologically ‘cold’ cancers, like pancreatic cancer. In the Phase II IMAGE-1 Study of IMM-101 in combination with gemcitabine, clinical data indicate that IMM-101 is well-tolerated and effective and that it has the potential as a first-line treatment to prolong progression-free survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) when compared to gemcitabine alone. The study data also suggest a beneficial effect on survival in patients with metastatic PDAC. Immodulon is currently prioritizing the initiation of a Bayesian adaptive pivotal study for IMM-101 in PDAC that can be expanded to evaluate IMM-101 in other immunologically ‘cold’ tumours across multiple parallel arms.

On June 18, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported it will host the second part of its virtual KOL investor event series on Wednesday, June 26, 2024 at 10:00 AM ET. To register, click here (Press release, FibroGen, JUN 18, 2024, View Source [SID1234644422]).

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The event will feature Rahul Aggarwal, M.D. (University of California San Francisco), who will discuss the unmet need and evolving treatment landscape for prostate cancer, as well as the clinical development program for FG-3246* (also known as FOR46), a CD46 targeting antibody-drug conjugate (ADC) with first-in-class potential for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The initiation of a Phase 2 monotherapy trial in mCRPC is expected in the second half of 2024.

The event will additionally review data from the Phase 1b/2 study evaluating FG-3246 in combination with enzalutamide in mCRPC presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting.

A live question and answer session will follow the formal presentation.

This series is intended for investor audiences only.

About Rahul Aggarwal, MD
Rahul Aggarwal, MD is a Professor of Medicine and Thomas Perkins Distinguished Professor of Cancer Research at the University of California San Francisco. He is the Associate Director for Clinical Research in the UCSF Helen Diller Family Comprehensive Cancer Center and the Program Leader for the Genitourinary Oncology program. He specializes in translational and clinical research in prostate cancer, with a particular emphasis on the development of novel therapeutic and imaging modalities for men with advanced prostate cancer. He has led numerous phase 1, 2, and 3 clinical trials in prostate cancer across a number of treatment modalities including small molecule targeted therapies, radioligand therapies, antibody-drug conjugates, and bi-specific T cell engagers.

About FG-3246
FG-3246 (FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and potentially other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1b/2 study being conducted at UCSF as an investigator-sponsored trial to evaluate FG-3246 in combination with enzalutamide. An additional investigator-sponsored radiopharmaceutical marker trial using a zirconium-89 positron emission tomography (PET) tracer for CD46 that utilizes the YS5 antibody is also underway at UCSF. The initiation of the Phase 2 monotherapy trial in metastatic castration-resistant prostate cancer is anticipated in the second half of 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.