On May 25, 2023 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics to selectively engage and modulate disease-specific T cells directly within the patient’s body, reported the presentation of a positive data update from its ongoing Phase 1 clinical trials evaluating its lead biologic from the IL-2-based CUE-100 series, CUE-101, for the treatment of patients with human papilloma virus (HPV16+) recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) as a monotherapy and in combination with pembrolizumab (Press release, Cue Biopharma, MAY 25, 2023, View Source [SID1234632092]). The data will be presented in a poster by Dr. Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center on June 5, 2023 at the ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, IL. In addition, the poster will also be highlighted by an expert head and neck cancer panel during a Poster Discussion Session immediately following the scheduled poster presentation.

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"CUE-101 clinical data to date continues to demonstrate both promising evidence of single-agent activity as well as complementary activity in combination with checkpoint inhibitor pembrolizumab." said Matteo Levisetti, M.D., chief medical officer of Cue Biopharma. "Based on the strength of the data to date, we believe CUE-101 has the promise to be a potential therapeutic advancement for patients battling head and neck cancer, a devastating disease of unmet medical need, with potential registrational paths both as monotherapy and in combination with pembrolizumab."

Key data highlights from the Phase 1b trial in combination with pembrolizumab at the RP2D of 4mg/kg, with 14 evaluable patients as of the data cutoff date of May 15, 2023 include:

Overall response rate of ~40% with 4 out of 5 confirmed PRs occurring in tumors with low PD-L1 expression as evidenced by combined positive scores (CPS) of 20 or less
Importantly, all 5 patients with a confirmed PR demonstrated >99% reduction in circulating cell-free HPV DNA (HPV cfDNA)
Median duration of response is 35 weeks with a median progression free survival (PFS) approaching 5 months
Key data highlights from the Phase 1b CUE-101 monotherapy patient expansion portion of the trial at the RP2D of 4mg/kg to date, include:

Current mOS approaching 14 months compares favorably to the historical mOS of 7.5 and 8.4 months reported from third-party clinical trials with checkpoint inhibitors in 2L R/M HNSCC in CheckMate 1411 and KEYNOTE-040 respectively2
CUE-101 has been well tolerated to date as monotherapy and in combination with pembrolizumab
Durable PR greater than 9 months and 6 DSD including a patient remaining on therapy for ~2 years, resulting in an overall clinical benefit rate of 35%
Dan Passeri, chief executive officer of Cue Biopharma, added, "Overall, the emerging data supports the potential of CUE-101 to provide patients with an enhanced disease control rate. We look forward to continuing to evaluate responses in these patients in addition to assessing the registrational trial options for CUE-101. Furthermore, the observed evidence of single agent activity in late-stage patients and the complementary mechanism of action in combination with checkpoint inhibition holds the potential to enhance anti-tumor activity across a broad range of cancers with our Immuno-STAT platform."

Presentation Details
Title: A phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer.
Abstract Number: 6013
Session: Head and Neck Cancer
Poster Session Display Date and Time: June 5, 2023, 1:15 PM-4:15 PM CDT
Presenter: Christine Chung, M.D., Moffit Cancer Center
Poster Discussion Session Date and Time: June 5, 2023, 4:30 PM-6:00 PM CDT
Discussant: Erminia Massarelli, M.D., Ph.D., City of Hope Comprehensive Cancer Center

The poster will be available in the Investor & Media section of the Company’s website at www.cuebiopharma.com under Scientific Publications and Presentations, following the presentation.

The Company will host an Investor Update call on Wednesday, June 14, 2023 to review and discuss the clinical progress and associated data presented at ASCO (Free ASCO Whitepaper) on June 5. Call details will be issued prior to the event.

References:
1. Ferris, R.L. (Oct 2016) Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck (CheckMate-141): a randomized, open-label, phase 3 study. The New England Journal of Medicine 2016; 375:1856-67.DOI: 10.1056/NEJMoa1602252

2. Cohen, EW E. (Nov 2018) Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomized, open-label, phase 3 study. The Lancet, DOI: View Source(18)31999-8

About ASCO (Free ASCO Whitepaper)
Founded in 1964, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Inc. (ASCO) (Free ASCO Whitepaper) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO (Free ASCO Whitepaper) represents nearly 45,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality, equitable patient care, ASCO (Free ASCO Whitepaper) works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. The ASCO (Free ASCO Whitepaper) Annual Meeting is a unique and unparalleled opportunity to connect with one of the largest, most diverse audiences in global cancer care as well as global cancer experts and professionals, to discover the latest innovations in cancer research and education.

About HPV+ Recurrent or Metastatic Head and Neck Cancer
Head and neck squamous cell carcinomas (HNSCC) are the 8th most common cancer in the world. A significant subset of the cases of HNSCC includes human papillomavirus (HPV) associated oropharyngeal tumors, with HPV16 detectable in 80%-90% of these cases. Despite the current standard of care treatments, more than 50% of patients with advanced HNSCC will experience recurrence, representing a significant unmet need.

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

On May 25, 2023 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development, and global access to life-changing radiopharmaceuticals, reported an upcoming poster presentation for the Company’s ongoing phase 1, pan-cancer, fibroblast activation protein-α (FAP-α)-targeted trial, FRONTIER (NCT05432193), at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023, in Chicago, IL (Press release, Point Biopharma, MAY 25, 2023, View Source [SID1234632090]).

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The Trial-in-Progress poster will include trial background information, study design considerations, and a cohort enrollment status update.

Presentation details are as follows:

Title: FRONTIER: FAPi radioligand open-label, phase 1 study to evaluate safety, tolerability and dosimetry of [Lu-177]-PNT6555—A dose escalation study for treatment of patients with select solid tumors

Presenter: Lisa Bodei, MD, PhD, Attending Physician, Director, Targeted Radionuclide Therapy, Molecular Imaging and Therapy Service at Memorial Sloan Kettering Cancer Center

Abstract Number: TPS3161

Session Name: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Session Date: Saturday, June 3rd

Presentation Time: 8:00 – 11:00 AM CT

Poster Board #: 355a

The associated abstract will be published by ASCO (Free ASCO Whitepaper) on meetings.asco.org at 5:00 PM ET on May 25. The full poster will become available to registered meeting attendees on Saturday, June 3rd at 8:00 AM CT / 9:00 AM ET. The poster will concurrently be archived on POINT’s Investor Relations website View Source

About the FRONTIER Trial

The FAPi Radioligand OpeN-label, phase 1 study to evaluate safety, Tolerability, and dosImetry of [Lu-177]-PNT6555; a dose Escalation study for tReatment of patients with select solid tumors (FRONTIER) trial is an open-label, phase 1 trial to evaluate safety, tolerability, and dosimetry of [Lu-177]-PNT6555 and [Ga-68]-PNT6555, the lead assets of the PNT2004 program. The trial commenced in summer 2022 in Canada and uses a [Ga-68]-based PNT6555 molecular imaging agent to select participants to receive a no-carrier-added (n.c.a.) [Lu-177]-based PNT6555 therapeutic agent. FRONTIER is designed to enroll up to 30 participants across seven FAP-avid cancer indications: colorectal cancer, adenocarcinoma of the pancreas, esophageal cancer, melanoma skin cancer, soft tissue sarcoma, cholangiocarcinoma, and head and neck cancer. Dose level cohorts 1 and 2 have been completed without dose-limiting toxicity. Enrollment to dose level cohort 3 (12 GBq) began in May 2023. We anticipate data from the full FRONTIER study to be available in the first half of 2024.

On May 25, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that the first participant has been dosed in an investigator-sponsored Phase 2 trial of oral rigosertib plus the PD-1 inhibitor pembrolizumab in patients with metastatic melanoma who have progressed on prior PD-1/L1 inhibitor therapy (Press release, Onconova, MAY 25, 2023, View Source [SID1234632089]).

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"There is an urgent need for new treatment approaches in metastatic melanoma, as 40 to 60% of these patients currently see little to no clinical benefit from PD-1 inhibitors," said Ann Richmond, Ph.D., Ingram Professor of Pharmacology and Medicine at the Vanderbilt University School of Medicine and Senior Research Career Scientist at TVHS, Department of Veterans Affairs (Nashville). "The limited efficacy of these agents is often due to ‘cold’ tumor microenvironments (TME) that prevent the infiltration of immune effector cells. Peer-reviewed preclinical studies1 suggest rigosertib can enhance the efficacy of immune checkpoint blockade in metastatic melanoma by reversing cold TMEs, providing a strong scientific rationale for this clinical trial."

Douglas B. Johnson, M.D., M.S.C.I., Associate Professor of Medicine of Hematology/Oncology at Vanderbilt University Medical Center and Principal Investigator of the trial commented, "Rigosertib combined with anti-PD-1 therapy has shown clinical activity in checkpoint inhibitor refractory lung cancer patients, and we believe this promising finding may translate to melanoma. The newly initiated Phase 2 study has been thoughtfully designed to begin exploring this hypothesis and will afford participants the opportunity to receive a novel therapeutic combination that may lead to improved clinical outcomes. I look forward to conducting the study and to the important scientific insights I expect it will provide."

The investigator-sponsored Phase 2 trial is an open-label, two-stage, single arm study. Stage 1 of the trial is expected to include ten patients. If a pre-specified response criteria is met, the study will then proceed to Stage 2, during which an additional 19 patients are expected to be enrolled. Patients in the study will receive 560 mg of oral rigosertib twice daily on days 1-21 of 28-day treatment cycles, plus 400 mg of pembrolizumab administered via intravenous infusion every six weeks. The primary endpoint of the trial is overall response rate, while key secondary endpoints include assessments of safety, tolerability, progression-free survival, and overall survival. Correlative biomarker assessments will also be conducted.

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, "Rigosertib’s investigator-sponsored trials are an important component of our corporate strategy that allows us to diversify the indications studied with our pipeline while remaining internally focused on our lead narazaciclib program. We are thrilled to be collaborating with Vanderbilt’s world-class physician-scientists on this latest trial and look forward to its advancement."

For additional information on the Phase 2 trial, see Clincialtrials.gov identifier NCT05764395.

On May 25, 2023 Xilio therapeutics presented its corporate presentation (Presentation, Xilio Therapeutics, MAY 25, 2023, View Source [SID1234632086]).

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On May 25, 2023 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported updated data from Part A of the ongoing registration-directed RAMP 201 (ENGOTov60/GOG3052) trial evaluating the safety and efficacy of avutometinib (VS-6766) alone and in combination with defactinib among patients with recurrent low-grade serous ovarian cancer (LGSOC) (Press release, Verastem, MAY 25, 2023, View Source [SID1234632085]).

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In the RAMP 201 study, treatment with the combination of avutometinib and defactinib resulted in an objective response rate (ORR) of 45% (13/29) and tumor shrinkage in 86% (25/29) of evaluable patients. Safety and tolerability continued to be favorable and consistent with previously reported data. These data, which will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, build on the Breakthrough Therapy Designation granted by the U.S. Food and Drug Administration (FDA) for the combination in recurrent LGSOC.

RAMP 201 is an international registration-directed Phase 2 study evaluating the safety and efficacy of avutometinib (VS-6766) alone and in combination with defactinib among patients with recurrent LGSOC. The key objectives of Part A (Selection Phase) of the RAMP 201 LGSOC study were to select avutometinib monotherapy or the combination of avutometinib and defactinib as the go forward regimen to be studied in Part B (Expansion Phase) of the study, and to assess efficacy in both KRAS mutant and KRAS wild type LGSOC. These data reinforce the selection of the combination of avutometinib (3.2 mg PO twice weekly 21/28 days) with defactinib (200 mg PO BID 21/28 days) as the go forward regimen regardless of KRAS status, and target enrollment has been achieved in both Part A and Part B.

"These results demonstrate avutometinib in combination with defactinib can deliver high response rates for patients with recurrent LGSOC with a promising safety profile to date," said Dr. Susana Banerjee, MBBS, MA PhD, FRCP, global and lead investigator of the study, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women’s Cancers at The Institute of Cancer Research, London. "It is particularly encouraging to see extensive tumor shrinkage in women who have had several treatment lines, including prior MEK inhibitors. These latest findings suggest the combination

may offer a new treatment option for women with this hard-to-treat cancer, and we are hopeful it will become the new standard of care."

Updated Results of Avutometinib and Defactinib Combination in RAMP 201 Part A

In Part A of the RAMP 201 trial, 31 patients with recurrent LGSOC were treated with the combination of avutometinib and defactinib, of which 29 were evaluable for efficacy with a minimum follow-up of 12 months and 13 patients remain on study treatment.

Overall, patients were heavily pretreated with a median of 4 prior systemic regimens (up to 11), including prior platinum-based chemotherapy, endocrine therapy and bevacizumab in most patients and prior MEK inhibitor therapy in about 13% of patients. Confirmed objective response rates (ORR) by blinded independent central review of 45% (13/29; 95% CI: 26%-64%) were observed.​ Tumor shrinkage was observed in the majority of patients, 86% (25/29). Further, 3 out of 4 patients who received prior MEK inhibitors responded to the combination.

Among the patients with KRAS mutant LGSOC, the ORR was 60% (9/15) in the combination arm. Among the patients with KRAS wild type LGSOC, the ORR was 29% (4/14). The median time to response was 5.5 months (range 1.6-14.7 months). The median duration of response and median progression free survival have not been reached.

The safety profile was consistent with previously reported safety data. The most common treatment-related adverse events for the combination in all treated patients (n=81) were nausea and vomiting, diarrhea, blood creatine phosphokinase (CPK) increased, peripheral edema, vision blurred, dermatitis acneiform and rash, fatigue, and dry skin, most of which were mild to moderate. The discontinuation rate, due to ≥ 1 adverse event, was 12% in the trial overall to date (4.9% due to elevated blood CPK).

"There are currently no treatments that are FDA or EMA approved specifically for the treatment of LGSOC, and this is clearly an area of unmet need. These results indicate that the combination of avutometinib and defactinib shows promise as a tolerable treatment with impressive response rates for women with recurrent LGSOC. Importantly, high response rates were seen both in women with and without KRAS mutations," said Rachel N. Grisham, M.D., Section Head, Ovarian Cancer and Director, Westchester Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center NY, and the study’s principal US investigator. "We look forward to the future outcomes from this important trial and improving care for women with LGSOC."

Regulatory Update

The Company plans to include mature data from RAMP 201, the Verastem sponsored clinical trial, and the investigator-sponsored FRAME study to support filing for accelerated approval. The Company is finalizing the design of a randomized confirmatory trial with the FDA, which is planned to begin in the second half of 2023.

Dr. Banerjee and Dr. Grisham have consulting relationships with Verastem Oncology.

About Avutometinib (VS-6766)

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

In contrast to other MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

About Low-Grade Serous Ovarian Cancer (LGSOC)

LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 30% of cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.

About RAMP 201

Verastem Oncology has initiated a Phase 2 registration-directed trial evaluating avutometinib alone and in combination with defactinib in patients with recurrent LGSOC as part of RAMP (Raf And Mek Program). RAMP 201 (ENGOTov60/GOG3052) is an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT) and the Gynecologic Oncology Group (GOG) and sponsored by Verastem Oncology. It is an adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent LGSOC. The first part of the study will determine the optimal regimen of either avutometinib monotherapy or in combination with defactinib in patients with recurrent LGSOC randomized 1:1 in each treatment arm. The determination of which regimen to take forward into the expansion phase of the trial will be made based on objective response rate data. The expansion phase of the study will examine efficacy and safety parameters of the regimen selected.