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Synthekine Presents Positive Initial Results from Phase 1 Clinical Trial of CD19 CAR-T (SYNCAR-001) and Orthogonal IL-2 (STK-009) Combination Therapy for Treatment of Hematologic Malignancies at ASH 2024 Annual Meeting

On December 09, 2024 Synthekine Inc., an engineered cytokine therapeutics company, reported positive initial results from a first-in-human Phase 1 study (NCT05665062) of SYNCAR-001 + STK-009 for the treatment of relapsed or refractory CD19+ hematologic malignancies (Press release, Synthekine, DEC 9, 2024, View Source [SID1234648958]). In the results presented from 8 patients treated in the dose escalation portion of the study with a fixed SYNCAR-001 infusion of 30M cells and STK-009 doses ranging from 1.5 to 6 mg, this combination therapy was well tolerated with no dose-limiting toxicities (DLTs) or IL-2-related toxicities observed. This regimen also demonstrated durable responses, including complete responses in all 4 patients with non-Hodgkin lymphoma (NHL).

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The data were presented by Lia Palomba, M.D., Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego. The poster will also be part of the ASH (Free ASH Whitepaper) Poster Walk on Blood Immunology & Cellular Therapy: Advancing Innovations and Translational Insights hosted by Blood Immunology & Cellular Therapy today from 7:30 a.m. to 8:30 a.m. PT.

"Enhancing CAR-T cells with consistent cytokine support, particularly IL-2, has the potential to significantly improve their therapeutic effect. However, prolonged wild-type IL-2 administration is currently not feasible due to severe toxicities like capillary leak syndrome (CLS)," said Dr. Palomba. "SYNCAR-001 + STK-009 represents an innovative solution, enabling the targeted delivery of a potent and durable IL-2 signal specifically to CAR-T cells in vivo and avoiding activation and proliferation of native lymphocytes that can cause CLS. Based on the data presented at ASH (Free ASH Whitepaper), we are encouraged by SYNCAR-001 + STK-009’s favorable safety and efficacy profile and its potential to treat patients with relapsed or refractory B cell malignancies."

SYNCAR-001 + STK-009 is a cytokine-enabled cell therapy regimen based on Synthekine’s proprietary orthogonal IL-2 technology. It is a two-component therapy consisting of SYNCAR-001, an autologous CD19-targeting chimeric antigen receptor T (CAR-T) cell which expresses an engineered IL-2 receptor, and STK-009, an engineered pegylated IL-2 cytokine that selectively signals through the engineered IL-2 receptor.

"The data presented at ASH (Free ASH Whitepaper) is important validation of our orthogonal IL-2 technology. Consistent with our preclinical observations, the combination of STK-009 and a low dose of SYNCAR-001 cells demonstrates robust cell expansion and persistence, potent cytotoxic activity, and durable cell fitness," said Debanjan Ray, chief executive officer of Synthekine. "We are excited to report that STK-009 selectively delivered IL-2’s proliferation and activation signal to SYNCAR-001 cells without the toxicities, including CLS, that are typically associated with wild-type IL-2 treatment. Furthermore, the ability of STK-009 to provide an IL-2 signal exclusively to SYNCAR-001 cells may allow us to bypass the need for potentially toxic lymphodepleting chemotherapy (LDC). We are now enrolling patients to this trial without LDC and have recently opened a trial in autoimmune diseases also without LDC."

SYNCAR-001 + STK-009 INITIAL PHASE 1 DOSE ESCALATION DATA IN CD19+ HEMATOLOGIC MALIGNANCIES

As of the October 8, 2024, data cutoff, 8 patients have been treated in the dose escalation portion of the study. Following a standard regimen of cyclophosphamide/fludarabine (cy/flu), patients received a fixed dose of 30 million SYNCAR-001 cells and doses of STK-009 at 1.5 mg (n=3), 3 mg (n=3) and 6 mg (n=2)
All patients were CAR-T naïve. Four patients had non-Hodgkin lymphoma (NHL) and four patients had chronic lymphocytic leukemia (CLL)
Complete response (CR) was observed in all 4 patients with NHL, and 1 patient with CLL had stable disease (SD) as best overall response
Responses were durable and ongoing in all 4 patients with NHL who exhibited CRs, with the longest duration of CR extending beyond 480 days
Majority of adverse events (AEs) were Grade 1 or 2; the most common AEs were cytopenias expected to occur with cy/flu treatment
Limited, mild-moderate cytokine release syndrome (CRS) was observed in 4 patients (maximum Grade 2); Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 1 patient
A high proportion of SYNCAR-001 cells sustain a long-lasting central memory phenotype on STK-009 treatment
Only minimal exhaustion and senescence of SYNCAR-001 cells was observed throughout the course of STK-009 treatment
In addition to this trial, a Phase 1 study (NCT06544330) of SYNCAR-001 + STK-009 in non-renal systemic lupus erythematosus and lupus nephritis is enrolling subjects, and received Fast Track designation from the U.S. Food and Drug Administration (FDA) in September 2024.

Guardant Health to Share New Research Demonstrating Value of Liquid Biopsy Tests, Real-world Data and AI Analytics in Tailoring Treatment Approaches for Breast Cancer at 2024 San Antonio Breast Cancer Symposium

On December 09, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company and its research collaborators will present data demonstrating the benefits of its precision oncology tests, real-world clinical-genomic database and AI analytics in optimizing therapy selection, identifying resistance mutations, and predicting long-term outcomes at the San Antonio Breast Cancer Symposium (SABCS) 2024 in San Antonio, Texas, Dec. 10-13, 2024 (Press release, Guardant Health, DEC 9, 2024, View Source [SID1234648957]).

Guardant and its research partners will present eight posters, including an SABCS Poster Spotlight featuring the use of the Guardant Reveal test, a tissue-free epigenomic assay, to investigate the dynamics of circulating tumor DNA (ctDNA) during neoadjuvant endocrine therapy in HR+ early breast cancer. Study findings suggest that ctDNA has the potential to provide valuable insights into tumor burden, sensitivity to endocrine therapy, and the emergence of endocrine resistance mutations. The investigators conclude that ctDNA could be a valuable tool in predicting long-term outcomes and in tailoring treatment approaches.

"Working together with our research collaborators, we continue to establish the important role of Guardant’s precision oncology portfolio in informing treatment selection and monitoring for recurrence and therapeutic response," said Craig Eagle, M.D., chief medical officer at Guardant Health. "We look forward to sharing new studies at SABCS that show how Guardant is working with researchers and cancer care teams to improve outcomes for people living with breast cancer."

Guardant Health and collaborator poster presentations at SABCS 2024

Wednesday, December 11 | 7:00-8:30 am | Hemisfair Ballroom 1-2

Abstract

Title

Product

PS7-05

SABCS Poster Spotlight

Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC)

GuardantINFORM

Wednesday, December 11 | 12:30 – 2:00 pm | Halls 2-3

P1-01-24

Genomic comparison of rapid vs. typical progressors on CDK4/6 inhibitor treatment in advanced breast cancer

GuardantINFORM

P1-05-30

A statistical model for integration of on-treatment circulating tumor DNA dynamics and prediction of outcomes in patients with ER+/HER2- metastatic breast cancer

Guardant Infinity

P1-10-05

Real-world molecular profiling after CDK4/6 inhibition in advanced breast cancer: analysis of the SOLTI-1903 HOPE study

Guardant360 CDx

Wednesday, December 11 | 5:30-7:00 pm | Halls 2-3

P2-05-20

Tissue-free minimal residual disease testing in 2,000 consecutive patients with breast cancer: real-world data and case report

Guardant Reveal

Thursday, December 12 | 7:00-8:30 am | Stars at Night 3-4

PS9-04

SABCS Poster Spotlight

Evaluating racial genomic differences in de novo metastatic breast cancer utilizing ctDNA: results from a large multi-center consortium

Guardant360

PS9-08

SABCS Poster Spotlight

Ultra-sensitive detection of circulating tumor DNA (ctDNA) in patients (pts) undergoing neoadjuvant endocrine therapy for hormone receptor-positive (HR+) early breast cancer (BC)

Guardant Reveal

Thursday, December 12 | 5:30-7:00 pm | Halls 2-3

P4-01-19

Clinical impact of MRD detection via ctDNA tumor-agnostic assay in early-stage breast cancer patients: a real-world experience

Guardant Reveal

The full abstracts for Guardant Health and a list of all abstracts being presented at SABCS 2024 can be found on the SABCS website.

For information and updates from the conference, visit booth 1424 and follow Guardant Health on LinkedIn, X (Twitter) and Facebook.

NeoGenomics to Present Key Research on Hematologic Malignancies at the 2024 American Society of Hematology Annual Meeting

On December 09, 2024 NeoGenomics, Inc. (NASDAQ: NEO), a leading oncology testing services company, reported the company will share its latest research on hematologic malignancies and the prognostic effects of microenvironment signatures in primary central nervous system (CNS) lymphoma at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, booth #2347, in San Diego, December 7-10 (Press release, NeoGenomics Laboratories, DEC 9, 2024, View Source [SID1234648956]). The company will also feature its robust hematological oncology solutions, including COMPASS, AML Express, and AML MRD Flow Panel.

"Our research at ASH (Free ASH Whitepaper) demonstrates that NeoGenomics continues to advance its leadership position in precision diagnostics for hematologic cancers," said Warren Stone, Chief Commercial Officer of NeoGenomics. "Through our collaboration with Duke University and the innovative work of our scientific team, we are uncovering critical insights into the genetic and microenvironmental factors that influence patient outcomes. These studies can potentially refine prognostic tools, align diagnostics with clinical guidelines, and ultimately improve therapeutic decision-making—enhancing care for patients battling blood cancer."

At the meeting, NeoGenomics will present a poster:

Neuronal-Glial and Immune Microenvironment Signatures Show Prognostic Effects in Primary CNS Lymphoma
Monday, December 9 at 6-8 p.m. PST
This study explores the prognostic effects of neuronal-glial and immune microenvironment signatures in primary central nervous system lymphoma. Through advanced multiplexing techniques, researchers have identified distinct microenvironment patterns with potential implications for predicting patient outcomes.
In addition to the poster, NeoGenomics’ two abstracts were recently published in the Blood supplement and archived on the ASH (Free ASH Whitepaper) and Blood abstracts site:

Genetic Insights into Myeloid Malignancies: A Comparative Analysis of NCCN Guidelines, the WHO Classification, and the ICC System
This study offers a comprehensive analysis of genetic insights into myeloid malignancies, comparing recommendations from major clinical guidelines and classifications, including the NCCN, WHO, and ICC systems.
A Prevalence Study of Gene Fusions in 2,958 Acute Myeloid Leukemia Patients from the Community Using FISH and NGS Testing
This prevalence study evaluates gene fusion occurrences in nearly 3,000 AML patients from community settings and utilizes FISH and NGS testing to uncover critical insights for diagnostic and therapeutic decision-making.
For more information about NeoGenomics’ research and presentations at ASH (Free ASH Whitepaper) 2024, visit www.neogenomics.com.

Opna Bio Announces Interim Data from Phase 1 Combination Study of OPN-2853 with Ruxolitinib in Patients with Advanced Myelofibrosis

On December 09, 2024 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology therapeutics, reported interim data from its lead clinical program, OPN-2853, in patients with advanced myelofibrosis showing encouraging levels of spleen reduction, with minimal toxicities and adverse events (Press release, Opna Bio, DEC 9, 2024, View Source [SID1234648955]). Preclinical data from a second program, OPN-6602, showed significant tumor regression in multiple myeloma models as a single agent and in combination with other therapeutics. The presentations took place this weekend at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting, December 7-10, 2024, in San Diego.

OPN-2853 Shows Spleen Reduction in Patients with Advanced Myelofibrosis

OPN-2853, a small molecule bromodomain and extra-terminal motif (BET) inhibitor, is being evaluated in an ongoing Phase 1 investigator-led study in patients with advanced myelofibrosis who are no longer responding to ruxolitinib alone. Myelofibrosis is a type of blood cancer that causes fibrosis in the bone marrow, anemia and enlarged spleen, amongst other symptoms. The study is testing three dose levels of OPN-2853 (20 mg, 40 mg and 80 mg), given orally once daily, in combination with ruxolitinib. As of February 2024, the cut-off date, 16 patients had been enrolled at different dose levels, across multiple sites in the United Kingdom, coordinated by the Cancer Research UK (CRUK) Clinical Trials Unit at the University of Birmingham.

In 12 evaluable patients, the median spleen size was reduced from baseline with spleens no longer palpable in 50% of evaluable patients. The combination dose has been well tolerated, and the majority of patients have completed eight cycles of combination treatment.

"We are very encouraged by these data to date, which demonstrate that daily dosing of OPN-2853 in combination with ruxolitinib was well tolerated, and showed spleen reduction in patients with myelofibrosis who have very limited options once they have progressed," said principal investigator Adam Mead, PhD, MRCP, FRCP, professor of hematology at the University of Oxford and CRUK senior cancer research fellow. "We are enthusiastic about the OPN-2853 and ruxolitinib combination and expect to have a recommended Phase 2 dose in early 2025."

Opna Bio is planning further clinical development with OPN-2853.

OPN-6602 Combinations Demonstrate Complete Tumor Regression in Preclinical Multiple Myeloma Models

OPN-6602, an oral, small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP), is currently being tested in a Phase 1 trial in patients with multiple myeloma (MM). MM is a type of blood cancer derived from malignant plasma cells in the bone marrow.

In MM mouse xenograft models, OPN-6602 showed 71% tumor suppression as a single agent, and 100% tumor regression when combined with dexamethasone, pomalidomide or mezigdomide with a sustained duration of response. RNA sequencing of treated tumors showed that OPN-6602 downregulated key MM driver and signature genes, and has the potential to overcome resistance mechanisms to standard-of-care regimens.

"We are very encouraged by the strength of the OPN-2853 clinical and OPN-6602 preclinical data, which highlights the potential of their unique pharmacokinetic profiles and validates our ‘safety by design’ approach. Both drug candidates have a high Cmax and short half-life, which allows for continuous daily dosing and effective target engagement with rapid clearance to mitigate toxicities," said Gideon Bollag, PhD, co-founder and chief scientific officer of Opna Bio. "This confers a significant advantage to these drugs when used as single agents and a potentially synergistic effect when used in combination with other therapies."

Belantamab Mafodotin shows significant overall survival benefit, reducing the risk of death by 42% in multiple myeloma at or after first relapse

On December 09, 2024 GSK plc (LSE/NYSE: GSK) reported statistically significant and clinically meaningful overall survival (OS) results from a planned interim analysis of the DREAMM-7 trial evaluating belantamab mafodotin in combination with bortezomib plus dexamethasone (BVd) versus daratumumab in combination with bortezomib plus dexamethasone (DVd) as a second line or later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, DEC 9, 2024, View Source [SID1234648954]). These data were featured today in an oral presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

The OS findings from DREAMM-7 build on previous data from the DREAMM-71 and DREAMM-82 trials, which showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for both belantamab mafodotin-based combinations versus standard of care comparators.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "The compelling overall survival data from the DREAMM-7 trial establish the potential of belantamab mafodotin in combination to significantly extend the lives of patients with multiple myeloma at or after first relapse. This represents an important advancement that could redefine the treatment of relapsed or refractory multiple myeloma."

With a median follow up of 39.4 months, the analysis presented today shows a statistically significant 42% reduction in the risk of death among patients receiving the belantamab mafodotin combination (n=243) versus the daratumumab-based comparator (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Although the median overall survival (mOS) was not reached in either arm of the study, the projected mOS for BVd is 84 months compared to 51 months for DVd.3

The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm. The survival benefit favoring BVd was seen as early as four months and was sustained over time as illustrated by the separation of the lines in the Kaplan-Meier curve shown above.

María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical Trials Unit, Hematology Department and Professor of Medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, said: "The totality of evidence from DREAMM-7 represents a potential paradigm shift for multiple myeloma patients who have experienced a relapse or become refractory to initial treatment. The OS results shown with the belantamab mafodotin combination in DREAMM-7 further cement the potential of this regimen to prolong the lives of patients with relapsed or refractory multiple myeloma compared to a standard of care daratumumab combination."

The belantamab mafodotin combination also showed statistically significant superiority on the key secondary endpoint of minimal residual disease (MRD) negativity (no detectable cancer cells) compared to the daratumumab combination. The greater than 2.5-fold improvement in the rate of MRD negativity seen at the time of the primary analysis for patients who received BVd can now be declared as statistically significant (p<0.00001) after the positive OS readout based on the predefined testing procedure. This further underscores the transformative potential of this belantamab mafodotin combination for multiple myeloma patients at or after their first relapse.

In addition to OS and MRD negativity, the belantamab mafodotin combination resulted in clinically meaningful improvements in all key secondary efficacy endpoints compared to the daratumumab combination, including duration of response (DOR) and progression-free survival 2 (PFS 2). The results indicate deeper and more durable responses among patients treated with BVd compared to DVd.

The safety and tolerability of the belantamab mafodotin regimen were consistent with the primary analysis and known safety profile of the individual agents. Grade 3 or higher adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively included thrombocytopenia (56% versus 35%; 34 versus 25 patients/100 person-years); anemia (9% versus 10%; exposure-adjusted rate [per 100 person-years] not reported); and neutropenia (14% versus 10%; 8 versus 7 patients/100 person-years).

Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally manageable and resolvable with dose modification, and led to a low (10%) treatment discontinuation rate.

Full data summaries for OS and other key secondary endpoints are shown below.

Key Secondary Endpoints
Endpoint

belantamab mafodotin +
bortezomib + dexamethasone (BVd)
n=243

daratumumab +
bortezomib + dexamethasone (DVd)
n=251

OS (overall survival), HR (95% CI)

0.58 (0.43-0.79)

P-value1

p=0.00023

OS, median (95% CI), months

NR (NR-NR)

NR (41.0-NR)

OS rate at 24 months, % (95% CI)

79% (73-84)

67% (61-73)

OS rate at 36 months, % (95% CI)

74% (68-79)

60% (54-66)

MRD (minimal residual disease) negativity rate for patients with CR or better, % (95% CI)

25.1% (19.8-31.0)

10.4% (6.9-14.8)

ORR (overall response rate), % (95% CI)

83.1% (77.8-87.6)

71.3% (65.3-76.8)

CR (complete response), or better, % (95% CI)

35.8% (29.8-42.2)

17.5% (13.0-22.8)

VGPR (very good partial response), or better, % (95% CI)

66.3% (59.9-72.2)

46.2% (39.9-52.6)

Median DOR (duration of response) (95% CI), months

40.8 (30.5-NR)

17.8 (13.8-23.6)

Median PFS 2 (progression-free survival 2), months

NR (45.6-NR)

33.4 (26.7-44.9)

0.59 (0.45-0.77)

1One-sided p-value based on stratified log-rank test.

In 2024, regulatory filings for belantamab mafodotin combinations for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials have been accepted in the US4, European Union5, Japan6 (with priority review), China (for DREAMM-7 only, with priority review; Breakthrough Therapy Designation7 also granted), United Kingdom, Canada and Switzerland (with priority review for DREAMM-8).

About the DREAMM clinical development program

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development program continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. In addition to DREAMM-7 and DREAMM-8, a phase III study in newly diagnosed transplant ineligible multiple myeloma, DREAMM-10, is expected to be initiated by the end of 2024.

About DREAMM-7

The DREAMM-7 phase III clinical trial is a multi-center, open-label, randomized trial evaluating the efficacy and safety of belantamab mafodotin in combination with bortezomib plus dexamethasone (BVd) compared to a combination of daratumumab and bortezomib plus dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.

A total of 494 participants were randomized at a 1:1 ratio to receive either BVd or DVd. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.

The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

Results from DREAMM-7 were first presented1 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About multiple myeloma

Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.8,9 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.10 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.11 Many patients with multiple myeloma, including approximately 65% in the US, are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic center.12,13,14

About belantamab mafodotin

Belantamab mafodotin is an investigational antibody-drug conjugate comprising a humanized B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.