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 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, reported to have entered into an exclusive worldwide license and collaboration agreement with Novartis Pharma AG, a subsidiary of Novartis AG (NYSE: NVS) (Press release, Ratio Therapeutics, NOV 18, 2024, View Source [SID1234648475]). The collaboration leverages Ratio’s radioligand therapy discovery and development expertise as well as its technology platforms for the development of a Somatostatin Receptor 2 (SSTR2) radiotherapeutic candidate for cancer.

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"The team at Ratio is honored and excited to partner with Novartis on the development of a next-generation SSTR2-targeting therapeutic," said Jack Hoppin, Ph.D., Chief Executive Officer of Ratio. "Together, we aim to develop a best-in-class therapy in the fight against SSTR2-expressing tumors."

"Radioligand therapies hold transformative potential for certain forms of cancer, and Novartis is committed to maximizing their impact by continually improving the benefit for patients," said Fiona Marshall, President of Biomedical Research at Novartis. "We are delighted to collaborate with Ratio to advance this RLT candidate and work together to bring forward additional therapeutic options for patients with difficult-to-treat cancer."

Under the terms of the agreement, Ratio will receive combined upfront and potential milestone payments up to $745m, and is eligible to receive tiered royalty payments. Ratio will collaborate with Novartis to drive preclinical activities to research and select an SSTR2-targeting development candidate. Novartis will assume responsibility for all remaining development, manufacturing, and commercialization activities.

The collaboration combines the expertise and strengths of Ratio and Novartis to further elevate the safety and efficacy of radiopharmaceuticals for patient benefit.

Chestnut Partners served as exclusive financial advisor to Ratio for this transaction.

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 European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) reported to have adopted a positive opinion recommending the approval of Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) (Press release, Sanofi, NOV 18, 2024, View Source [SID1234648476]). A final decision is expected in the coming months.

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Dietmar Berger, M.D., Ph.D.

Chief Medical Officer, Global Head of Development at Sanofi

"The positive CHMP opinion is an important step forward for people with transplant-ineligible newly diagnosed multiple myeloma for whom effective front-line therapy may improve long-term outcomes. If approved, this Sarclisa-based combination could establish a new standard-of-care treatment approach for patients in the EU, helping to address a critical care gap in multiple myeloma treatment, and reinforcing Sarclisa’s potential as the anti-CD38 therapy of choice."

In September 2024, the US Food and Drug Administration (FDA) approved Sarclisa in combination with VRd for the treatment of adult patients with NDMM who are not eligible for ASCT, representing the first global approval for Sarclisa in the first line setting. In addition, the FDA granted orphan drug exclusivity for Sarclisa in the approved indication.

Sarclisa is currently approved in two indications for the treatment of certain adult patients with relapsed or refractory MM in more than 50 countries, including the US and EU.

First positive global phase 3 study combining anti-CD38 therapy with VRd to significantly improve PFS versus VRd alone in transplant-ineligible NDMM supports CHMP decision

The positive CHMP opinion is based on data from the IMROZ phase 3 study, which was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 annual meeting, European Hematology Association (EHA) (Free EHA Whitepaper) 2024 meeting, and published in The New England Journal of Medicine. IMROZ is the first global phase 3 study of a CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve progression-free survival (PFS) versus VRd alone. The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals.

About Sarclisa

Sarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA.

Currently Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. In Europe, based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is also approved in combination with VRd as a first line treatment option for adult patients with NDMM who are not eligible for ASCT, based on the IMROZ phase 3 study.

Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. In addition, the company is evaluating a subcutaneous administration method for Sarclisa in clinical studies. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

On November 18, 2024 Cancer Targeted Technology (CTT), a privately-held Seattle-based biotechnology firm focusing on cancer diagnostics and therapeutics, reported that the National Cancer Institute awarded the Phase I portion ($400K) of the fast track Phase I/II ($2.4M) Small Business Innovation Research (SBIR) grant to develop a new drug to treat metastatic prostate cancer (Press release, Cancer Targeted Technology, NOV 18, 2024, View Source [SID1234648491]). The grant focuses on a promising new prodrug, CTT2274, that targets Prostate-Specific Membrane Antigen (PSMA) on prostate cancer and is designed to release a toxic drug, MMAE, within the cell that takes up the prodrug. PSMA is over-expressed on prostate cancer and expression increases as the cancer metastasizes and becomes castrate resistant. CTT’s unique phosphoramidate-based agents, bind irreversibly to PSMA and unlike other agents targeting PSMA, this distinctive mode of binding enhances uptake and internalization by tumor cells, leading to increased accumulation of the therapeutic payload and improved efficacy.

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Studies to date using CTT2274 treatment of mice bearing human prostate tumors have shown remission of tumor growth and an overall increase in survival. In addition, because of the prodrug release within the tumor cells, safety of the drug, at doses that are effective at inhibiting or reversing tumor growth, is excellent. In the Phase I portion of the grant, to be completed in Q2 2025, CTT will conduct additional non-clinical efficacy studies and manufacturing optimization. In Phase II of the grant, to be completed in Q2, 2026, CTT will conduct additional manufacturing and safety assessments necessary to advance CTT2274 to an Investigational New Drug (IND) application. These IND studies will support the initial clinical trial in metastatic prostate cancer planned for 2026.

"CTT2274 has a unique structure and linker that maximizes tumor uptake and allows for release of the chemotherapeutic drug only within the tumor cell thus minimizing potential side effects from the chemotherapy. No other prodrug like this is being developed for prostate cancer and CTT2274 holds great promise as a future treatment for men suffering from prostate cancer." stated Dr. Beatrice Langton-Webster, CEO of CTT and Principal Investigator on the grant. Visit CTT’s website at View Source to learn more about CTT2274.