On November 18, 2024 Toragen Inc., a San Diego-based clinical-stage biotechnology company focused on developing uniquely selective drugs targeting cancers caused by viruses, reported positive safety data from its ongoing Phase 1 trial of TGN-S11, its small molecule drug candidate, in patients with HPV-associated cancers (Press release, Toragen, NOV 18, 2024, View Source [SID1234648490]).

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This Phase 1 trial is an open-label, non-randomized study in cohorts of patients with relapsed, resistant, or metastatic HPV-associated cancers. The study is being conducted in two parts: Part 1 is escalating doses of TGN-S11 monotherapy and Part 2 is TGN-S11 in combination with Keytruda, a PD-1 checkpoint inhibitor. The dose escalation part consists of up to five Cohorts of three to six patients on monotherapy with increasing doses of TGN-S11. The Keytruda combination part consists of up to five Levels of three to six patients with increasing doses of TGN-S11 and the standard dose of Keytruda.

In Part 1, 9 patients were treated with TGN-S11 as monotherapy in the first 3 dose cohorts with no safety issues identified. One-third of the patients in this portion of the study showed drug activity with decreases in tumor size and decreases in circulating tumor HPV DNA (ctHPV DNA). In addition, three patients have been treated in Part 2 Level 1 evaluating TGN-S11 in combination with Keytruda with no safety issues. Two of these 3 patients in this portion of the study showed drug activity with decreases in tumor size and decreases in circulating tumor HPV DNA. One of these 3 patients continues to receive combination therapy and has a 93% reduction in ctHPV DNA. The study is ongoing with patients currently being dosed in Part 1 Cohort 4 and Part 2 Level 2.

"We have been very pleased with the positive safety profile for TGN-S11 in patients who completed the first 3 monotherapy dose cohorts of Part 1 and the first level of Part 2 in combination with Keytruda in this ongoing Phase 1 trial," said Dr. Sandra Coufal, Toragen’s CEO. "The drug activity observed in 5 of these 12 subjects is also very encouraging. Based on the current progress, we believe both parts of the study will be completed by the end of 2024."

On November 18, 2024 Foresight Diagnostics, a leader in ultrasensitive minimal residual disease (MRD) testing, reported the presentation of multiple studies showcasing Foresight CLARITY MRD at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place December 7-10 in San Diego, California (Press release, Foresight Diagnostics, NOV 18, 2024, View Source [SID1234648489]).

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The presentations span various lymphoma types and treatment settings, demonstrating the broad applicability of the Foresight CLARITY MRD detection technology for monitoring treatment response and predicting patient outcomes. The studies include collaborations with multiple pharmaceutical companies and research institutions, including AstraZeneca, Bristol Myers Squibb (BMS), Daiichi Sankyo (DSI), Stanford University, Washington University, and others.

"These studies add to the growing body of evidence supporting ultra-sensitive MRD testing as a critical tool in lymphoma care and drug development," said David Kurtz, MD, PhD, Chief Medical Officer and Head of Research at Foresight Diagnostics. "We see in these studies that MRD measurement with Foresight CLARITY consistently enables earlier and more accurate treatment response assessment than conventional imaging-based methods. The ability to monitor disease status in real-time with ultra-sensitive MRD assays like Foresight CLARITY may help accelerate clinical trials and lead to more personalized decision-making for patient care."

Results utilizing Foresight CLARITY MRD technology are featured in six abstracts, including three that are co-authored by Foresight.

Presentation highlights include:

LBCL/DLBCL:

ctDNA-MRD as a surrogate endpoint for 2L CAR T – Analysis of the Phase 3 TRANSFORM trial in second-line treatment for large B-cell lymphoma (LBCL) reinforced the potential of circulating tumor DNA (ctDNA) as an earlier endpoint for response assessment and assessment of clinical trial results. In the TRANSFORM study, patients receiving lisocabtagene maraleucel (liso-cel) had significantly improved event-free survival compared to standard of care. Consistent with this result, patients receiving liso-cel also demonstrated higher rates of MRD clearance, demonstrating CLARITY’s ability to measure differential treatment responses.
MRD Response with novel first-line therapy in high-risk DLBCL – Analysis of a Phase 1b trial CC-220-DLBCL-001 combining golcadomide with R-CHOP in previously untreated aggressive B-cell lymphoma showed promising MRD clearance rates. The data demonstrated that 90% of patients achieved MRD negativity at end of treatment with golcadomide 0.4mg + R-CHOP, with strong responses observed even in high-risk patients. These data further support the ongoing Phase 3 GOLSEEK-1 study investigating this novel combination therapy in high-risk 1L LBCL.
Enhanced risk stratification by MRD vs. traditional methods – New research investigates the predictive value of the International Prognostic Index (IPI), currently the primary pre-treatment risk assessment tool for DLBCL. The study revealed that pre-treatment IPI scores did not significantly correlate with end-of-treatment MRD status, with MRD testing being a superior predictor of progression-free survival.
Follicular Lymphoma:

MRD-based response assessment of novel FL therapies – Two studies demonstrated the value of MRD assessment in follicular lymphoma trials, with new treatment approaches showing early clearance. The CD19xCD3 bispecific antibody AZD0486 achieved 89% MRD negativity in relapsed or refractory FL patients by 12 weeks in complete responders. In the 1L setting, the chemotherapy-free combination of mosunetuzumab and polatuzumab vedotin showed similar early MRD clearance, with 7 of 8 complete responders achieving MRD negativity before cycle 3. These results highlight the potential for MRD as an early indicator of therapeutic response in FL clinical trials.
PTCL:

ctDNA as a prognostic biomarker for T-cell lymphoma – Analysis from the VALENTINE-PTCL01 Phase 2 trial in relapsed/refractory peripheral T-cell lymphoma (PTCL) revealed that patients achieving early, deep ctDNA reduction (>5-fold decrease by Cycle 2 Day 1) experienced significantly longer progression-free survival, establishing ctDNA monitoring as a powerful tool for early response assessment.
Information on abstract presentation time and dates can be found below. To meet with Foresight Diagnostics, visit booth #3423 or contact us at [email protected].

Oral Presentations:

Circulating Tumor DNA (ctDNA) as an Early Outcome Predictor in Patients with Second-Line Large B-Cell Lymphoma After Lisocabtagene Maraleucel Versus Standard of Care Treatment from the Phase 3, Randomized TRANSFORM Study

Presenter: Ash Alizadeh, MD, PhD (Stanford University)
Session 628
Date/Time: Saturday, December 7, 2024, 10:45 a.m.
Sponsor: Bristol Myers Squibb
Co-authored by Foresight Diagnostics
Escalating Doses of AZD0486, a Novel CD19xCD3 T-Cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma

Presenter: Jing-Zhou Hou, MD, PhD (UPMC Hillman Cancer Center)
Session 623
Date/Time: Saturday, December 7, 2024, 5 p.m.
Sponsor: AstraZeneca
Golcadomide (GOLCA) Plus R-CHOP Has High Minimal Residual Disease (MRD) Negativity across High-Risk, Untreated Aggressive B-Cell Lymphoma (a-BCL)

Presenter: Jason R. Westin, MD (MD Anderson)
Session 627
Date/Time: Sunday, December 8, 2024, 12:30 p.m.
Sponsor: Bristol Myers Squibb
International prognostic index poorly predicts EOT ctDNA MRD status in DLBCL and has limited impact on its predictive value for outcomes

Presenter: Jordan S. Goldstein, MD, MS (Stanford University)
Session 626
Date/Time: Sunday, December 8, 2024, 5 p.m.
Co-authored by Foresight Diagnostics
Poster Presentations:

Prediction of Clinical Response by Phased Variants in Circulating Tumor DNA (ctDNA) in the VALENTINE-PTCL01 trial of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Presenter: Neha Mehta-Shah, MD, MSCI (Washington University)
Abstract #4342, Session 621
Date/Time: Monday, December 9, 2024, 6-8 p.m.
Sponsor: Daiichi Sankyo
Co-authored by Foresight Diagnostics
Mosunetuzumab Plus Polatuzumab Vedotin Induces Early Complete Responses in Previously Untreated High Tumor Burden Follicular Lymphoma

Presenter: David A Russler-Germain, MD, PhD (Washington University)
Abstract #4414, Session 623
Date/Time: Monday, December 9, 2024, 6-8 p.m.

On November 18, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported the opening of enrollment for the Phase 1 clinical trial evaluating ADI-270 in patients with metastatic/advanced clear cell renal cell carcinoma (ccRCC) (Press release, Adicet Bio, NOV 18, 2024, View Source [SID1234648488]).

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"Solid tumors represent one of the highest unmet medical needs in oncology and have yet to benefit from the breakthroughs observed with CAR T cell therapies in hematologic malignancies. Emerging data from ADI-270, our armored allogeneic ‘off the shelf’ gamma delta 1 CAR T cell therapy targeting CD70 positive cancers, have shown potential in addressing this gap," said Chen Schor, President and Chief Executive Officer. "At the recent ASGCT (Free ASGCT Whitepaper) conference, we presented preclinical data in which ADI-270 demonstrated significant tumor infiltration, resistance to the immunosuppressive tumor microenvironment, and potent activity via CAR and innate-mediated targeting, highlighting its potential for treating solid tumors. We look forward to enrolling patients and anticipate sharing preliminary clinical data from the trial in the first half of 2025."

About the Phase 1 Trial

The Phase 1 multicenter, open-label clinical trial is designed to investigate ADI-270 as monotherapy in adults with relapsed or refractory ccRCC. Following lymphodepletion, patients will be eligible to receive a single dose of ADI-270 with a starting dose level of 3E8 CAR+ cells. Subject to meeting protocol defined criteria, patients enrolled in the trial may be eligible to receive a second dose of ADI-270. The dose escalation and dose expansion portions of the trial will evaluate safety, tolerability, and pharmacokinetics as well as anti-tumor activity as assessed by overall response rate, duration of response and disease control rate.

About ADI-270

ADI-270 is an armored allogeneic "off-the-shelf" gamma delta CAR T cell therapy candidate targeting CD70-positive cancers. CD70 is a compelling target due to its high expression in both solid and hematological malignancies. ADI-270 is engineered with a third-generation CAR designed to target CD70 using its natural receptor, CD27, as the binding moiety and is further armored with a dominant negative form of the transforming growth factor-β receptor II (dnTGFβRII) to provide functional resilience to the immunosuppressive tumor microenvironment. ADI-270 is also designed to increase exposure and persistence by reducing susceptibility to host vs. graft elimination. These properties of ADI-270 combined with the potent tumor infiltration demonstrated with gamma delta 1 T cells aim to improve clinical responses of RCC patients and other patients with CD70+ tumors.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common tumor of the kidney, constituting 80% to 85% of primary renal neoplasms. Clear cell RCCs (ccRCC) are the most common subtype, accounting for 80% of all RCCs. ccRCC is an aggressive subtype arising from renal stem cells commonly arising in the proximal nephron and tubular epithelium, and often metastasizes to the lungs, liver, and bones. Approximately 20% of newly diagnosed cases of RCC are locally advanced or metastatic and up to 30% of patients will develop metastatic disease following nephrectomy. While the 5-year survival rate for localized RCC is 93%, the 5-year survival rate for advanced disease is 15%.

On November 18, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported the publication in Science Immunology of preclinical data demonstrating the potential of IPH6501, Innate’s proprietary NK cell engager including an IL-2v and targeting CD20 from the ANKET platform (Press release, Innate Pharma, NOV 18, 2024, View Source [SID1234648487]). IPH6501 is currently evaluated in a Phase 1/2 clinical trial in B-cell non-Hodgkin lymphoma (B-NHL) (NCT06088654).

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The data published shows that IPH6501, also called CD20-NKCE-IL2v in the publication, boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including those with low CD20 density. In vivo studies in nonhuman primates and tumor mouse models further validated its efficacy and revealed that IPH6501 induces peripheral NK cell migration at the tumor site.

"These new findings underscore the remarkable potential of IPH6501 to transform the treatment landscape for B-NHL. IPH6501 showed greater killing efficacy over a T cell engager targeting CD20 in in vitro preclinical models while presenting reduced toxicities compared with those commonly associated with T cell therapies. We are particularly encouraged by results that reveal IPH6501’s ability to drive NK cell migration directly to tumor sites, highlighting its potential as a game-changer in immuno-oncology. These findings are a testament to the promise of NK cell therapies to deliver safer and more targeted solutions for patients in need," commented Eric Vivier, DVM, PhD, Chief Scientific Officer of Innate Pharma.

The data published further support the current clinical development plan of IPH6501 in Relapsed/Refractory B-NHL.

About ANKET

ANKET (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer. This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer.

About IPH6501

IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not a subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells.

IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA (Free EHA Whitepaper) 2023, Carrette, SITC (Free SITC Whitepaper) 2024, Demaria et al, Science Immunology 2024).

IPH6501 is currently being evaluated in a Phase 1/2 multicenter trial (NCT06088654), investigating the safety and tolerability of IPH6501 in patients with Relapsed and/or Refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma.

On November 18, 2024 Bexion Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing a novel class of biologic therapy to treat solid tumor cancers and chemotherapy-induced peripheral neuropathy (CIPN), reported completion of enrollment in the open label portion of Phase 1b/2 ASIST study of BXQ-350 in combination with Standard-of-Care (SOC) for the first line treatment of metastatic colorectal cancer (mCRC) (Press release, Bexion, NOV 18, 2024, View Source [SID1234648486]).

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"I am delighted that Bexion has completed enrollment for its Phase 1b/2 clinical trial and am especially pleased my clinical site has made significant contributions toward this effort," said Reema A. Patel, MD, Associate Professor of Medicine at the Markey Cancer Center of the University of Kentucky. "BXQ-350’s mechanism of action lends itself to potential benefit in metastatic colorectal patients and peripheral neuropathy. Severe neuropathy is a key reason that patients drop off chemotherapy for colorectal cancer, and BXQ-350 has been shown to possess potential anti-neuropathy properties. I am excited by the potential of BXQ-350 to reduce or even potentially reverse neuropathic pain in these patients."

The ASIST study will assess the safety and efficacy of BXQ-350 plus SOC, modified FOLFOX7 (mFOLFOX7) and bevacizumab, in patients with newly diagnosed mCRC. The study is also evaluating whether the administration of BXQ-350 with mFOLFOX7 and bevacizumab may diminish CIPN, enabling participants to receive the total and planned doses of mFOLFOX7.

"We extend our gratitude to all the patients, clinical investigators, and site research staff who continue to contribute to the advances we are making," said Jim Beach, Chief Executive Officer of Bexion. "We are excited about advancing to the next stage of clinical development, including further discussions with FDA on study design, and we look forward to providing updates as we reach upcoming milestones in 2025."

More information about the clinical trial is available at clinicaltrials.gov (ASIST study; NCT05322590).

About BXQ-350
Bexion’s lead drug candidate is BXQ-350, a first-in-class biologic containing the multifunctional sphingolipid activator protein, Saposin C, and a phospholipid. Multiple Phase 1 clinical trials in adult and pediatric patients have demonstrated a robust safety profile for BXQ-350 with evidence of single agent activity across multiple solid tumor types. Additionally, other clinical and non-clinical data suggest BXQ-350 has activity in chemotherapy-induced peripheral neuropathy, an area of high unmet medical need in patients treated with oxaliplatin and other chemotoxic agents.