On May 25, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that it will present additional positive data from the ongoing Phase 1 study of MP0317, a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), at the 2023 ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) Annual Meeting, held June 2–6 in Chicago, Illinois (Press release, Molecular Partners, MAY 25, 2023, View Source [SID1234632094]).

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The data demonstrate that MP0317 shows evidence of tumor-localized CD40 activation (analyses in paired tumor biopsies). The detection of MP0317 in tumors positively correlated with immune activation when comparing high vs. low doses of MP0317. This detection was associated with a statistically significant CD40-mediated increase of antigen-presenting cells and interferon γ signature. Furthermore, MP0317 has demonstrated a favorable safety profile. The current data support planning of future combination studies.

"These positive data continue to demonstrate that MP0317’s unique mechanism of action has the potential to overcome the limitations of existing therapies that target CD40 by activating only in the tumor microenvironment and therefore avoid systemic toxicities seen by other treatments," said Nicolas Leupin, MD, Ph.D., Chief Medical Officer of Molecular Partners. "MP0317 encapsulates the advantages we believe we can achieve through our DARPin platform: to design candidates to overcome biological challenges that other drug classes like antibodies cannot address. These data of the ongoing study will further support the advancement of MP0317 into later-stage clinical research with partners and highlight the potential of MP0317 for evaluation in combination settings."

"Clinical data from 36 patients with advanced solid tumors, dosed across 8 dose levels, confirms that the tumor-FAP-targeted CD40 agonist MP0317 is safe and well tolerated with limited systemic inflammation compared to other CD40 agonists," said Dr Carlos Gomez-Roca, Head of the Early Phase & Clinical Research Unit at IUCT-Oncopole Claudius Regaud at Toulouse, France, and investigator on the study. "The analysis of paired pre- and on treatment tumor biopsies as well as peripheral biomarkers provides evidence of target occupancy and pharmacodynamic modulation in the tumor microenvironment, consistent with tumor localised CD40 activation. The current data enables further evaluation of MP0317 in combination."

This ongoing first-in-human Phase 1, open-label, dose-escalation study assesses the safety and tolerability as well as pharmacokinetics/pharmacodynamics and antitumor activity of MP0317 monotherapy in patients with refractory/relapsed solid tumors known to express FAP and CD40 (NCT05098405). To date, the 36 patients enrolled in the Netherlands and France across eight dosing cohorts received MP0317 at doses of 0.03–10 mg/kg in every-3-weeks [q3w] and weekly [q1w] schedules (data cut-off 02 May 2023).

MP0317 monotherapy was seen to result in tumor-localized CD40 activation: biomarker data confirmed presence of MP0317 in the tumors of patients with evaluable pre- and on-treatment biopsies as of the cutoff date. This detection of MP0317 in tumors positively correlates when comparing high vs. low doses of MP0317 and was associated with a statistically significant CD40-mediated increase of antigen-presenting cells as well as interferon γ production within the tumor microenvironment. To date, one patient achieved an unconfirmed partial response and stable disease was observed in 5 additional patients.

The observed safety profile of MP0317 monotherapy to date is favorable. A dose-limiting toxicity was reported in one patient (transient asymptomatic Grade 3 elevation of liver enzymes), at the highest planned MP0317 dose of 10 mg/kg administered q3w.

The positive results of this ongoing Phase 1 study in patients with refractory/relapsed tumors support continued clinical evaluation of MP0317 and potential investigation in combination studies. The study continues to enroll one more cohort (q1w). For further information please see clinicaltrials.gov (NCT05098405).

The details of the poster presenting these results from the ongoing Phase 1 study at the ASCO (Free ASCO Whitepaper) 2023 Annual Meeting can be found below. The poster will be made available on Molecular Partners’ website after the presentation.

Title: Phase I study of MP0317, a FAP-dependent DARPin, for tumor-localized CD40 activation in patients with advanced solid tumors
Poster Session: Developmental Therapeutics—Immunotherapy
Abstract number: 2584
Poster number: 426
Location & Timing: Hall A; June 3, 2023; 8:00–11:00am CDT
Authors & Affiliations:
C Gomez-Roca1, N Steeghs2, E Gort3, H De Winter4, E Fernandez 4, V Stavropoulou 4, N Stojcheva 4, P Baverel 4, J Krieg 4, K Ioannou 4, A Florescu 4, P Mossi 4, L Hoenig 4, B Baud-Berthier 4, V Kirkin 4, A Goubier 4, P Legenne 4, P Cassier5

About MP0317
MP0317 targets both the FAP and the immunostimulatory protein CD40 to enable tumor-localized immune activation. Through this proposed mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

On May 25, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported that it will present data from Cohort 1 of its pivotal trial SPEARHEAD-1 (NCT04044768) for people with advanced synovial sarcoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, Adaptimmune, MAY 25, 2023, View Source [SID1234632093]). The poster, titled "The SPEARHEAD-1 trial of afamitresgene autoleucel: Analysis of overall survival in advanced synovial sarcoma," will be presented by Dr. Brian Van Tine of the Washington University School of Medicine at 1:15 p.m. CDT, Saturday, June 3rd, in Hall A, Sarcoma track.

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Dr. John Charlson of the Medical College of Wisconsin and Adaptimmune clinical trial investigator: "Engineered T-cell therapies, like afami-cel, have the potential to change the way we manage difficult to treat late-stage cancers like synovial sarcoma. The current standard-of-care treatments for synovial sarcoma were approved more than two decades ago, have limited efficacy and their dosing schedules, and resulting side effects often negatively impact patients’ lives so there is a tremendous unmet need for novel, effective treatments."

Dennis Williams, Pharm.D., Adaptimmune’s SVP of Late-Stage Development: "There is a high unmet need in late-stage solid tumor cancers and synovial sarcoma is no exception. We have reported an impressive response rate of ~39% among heavily pre-treated patients with advanced synovial sarcoma. We are seeing very meaningful survival data, especially in people who have a response after a single dose of afami-cel. Afami-cel is intended to be our first commercial product and we are developing additional products for other late-stage solid tumors including ovarian, bladder, and head & neck cancers."

Patients with advanced synovial sarcoma who received a single dose of afami-cel had meaningful survival, especially those patients with a RECIST response
There were 44 people with advanced synovial sarcoma who received afami-cel in Cohort 1 of the SPEARHEAD-1 trial. The overall response rate (ORR) by independent review per RECIST v1.1 among people with synovial sarcoma was ~39% (as reported at CTOS 2022) with 17 patients responding. The median duration of response was approximately 12 months (95% CI: 4.44 – not estimable).

An interim analysis was performed on March 29, 2023, when the median (range) follow-up time was 27.8 (16-38) months. The median overall survival was approximately 17 months and overall survival (OS) was significantly longer in patients who had a RECIST response, compared to non-responders, with a 12-month OS probability of 90% and 24-month OS probability of 70%. Median OS among responders has not been reached.

Afami-cel is on path to be Adaptimmune’s first potential commercial product
Adaptimmune has completed submission of the preclinical (Part 1) and clinical modules (Part 2) of the Biologics License Application (BLA) for afami-cel for the treatment of synovial sarcoma, which is targeted for completion in mid-2023. This BLA is supported by data from Cohort 1 of the pivotal SPEARHEAD-1 trial, which has met its primary endpoint for efficacy. For afami-cel, the FDA has provided Orphan Drug Designation (ODD) for the treatment of soft tissues and Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of synovial sarcoma.

Overview of SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Approximately 90 patients were planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in both cohorts is complete. The primary efficacy analysis is for Cohort 1 only. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Key eligibility criteria: ECOG performance status of 0 or 1; HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and patients must have received either an anthracycline- or ifosfamide-containing regimen. Eligible patients received afami-cel doses between 1-10 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.

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.