On June 2, 2025 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that the Journal of Clinical Oncology has published the final analysis from the Phase 2 C-144-01 clinical trial evaluating the individualized T cell therapy Amtagvi (lifileucel) in patients with advanced melanoma (Press release, Iovance Biotherapeutics, JUN 2, 2025, View Source [SID1234653613]). These five-year follow-up results are being simultaneously presented during an oral session today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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This five-year analysis of the C-144-01 trial represents unprecedented durability and duration of follow-up in advanced melanoma patients previously treated with anti-PD-1 and targeted therapy, where applicable. The analysis includes 153 patients from cohorts 2 and 4 of the C-144-01 trial.

One-time Amtagvi treatment demonstrated long-term benefit in heavily pretreated patients, including deep and durable responses, meaningful overall survival without further treatment, and no new or late-onset adverse events at a median follow-up of 57.8 months. The objective response rate was 31.4% with a median time to response of 1.4 months and a median duration of response of 36.5 months. Nearly one third of responders (31.3%) completed the five-year assessment with ongoing responses. The median overall survival (mOS) was 13.9 months with a five-year survival rate of 19.7%. Survival outcomes were consistent among responders, regardless of time of onset of response to Amtagvi therapy.

The observed safety profile was consistent with that of nonmyeloablative lymphodepletion and interleukin-2 administration. The incidence of AEs decreased rapidly within the first two weeks after Amtagvi infusion, and there were no new or late-onset treatment-related AEs.

Theresa Medina, M.D., medical oncologist at the University of Colorado Cancer Center on the Anschutz Medical Campus, stated, "Amtagvi has demonstrated long-term benefit and meaningful overall survival in a difficult-to-treat melanoma patient population resistant to immune checkpoint inhibitor therapy. Five years following one-time Amtagvi treatment, responses persisted or deepened during an extended treatment-free interval for some patients. Amtagvi offers a new standard of care for the advanced melanoma community and sets a new bar for one-time cell therapies with curative intent in solid tumors."

In February 2024, the U.S. Food and Drug Administration granted accelerated approval to Amtagvi for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. The approval was based on overall response rate and duration of response from the C-144-01 clinical trial. With this approval, Amtagvi became the first one-time T cell therapy for a solid tumor cancer as well as the first approved treatment option for patients with advanced melanoma after anti-PD-1 and targeted therapy. Iovance is also conducting TILVANCE-301, a Phase 3 trial in frontline advanced melanoma to confirm clinical benefit.

About the C-144-01 Clinical Trial

C-144-01 is a global, multicenter Phase 2 study in which patients received treatment with lifileucel. The study enrolled patients with metastatic melanoma who were previously treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor. Efficacy was established on the basis of objective response rate (ORR) and duration of response (DOR) by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The pivotal Cohort 4 and supportive Cohort 2 of Study C-144-01 enrolled patients that met the same primary eligibility criteria, had the same assessments, and had received the same regimen and AMTAGVI that was produced using the same manufacturing process, and product formulation. The final five-year analysis of C-144-01 was published in the Journal of Clinical Oncology in 2025.

About Amtagvi

AMTAGVI is a prescription medicine used to treat adults with a type of skin cancer that cannot be removed surgically or has spread to other parts of the body called unresectable or metastatic melanoma.

AMTAGVI is used when your melanoma has not responded or stopped responding to a PD-1 blocking drug either by itself or in a combination, and if your cancer is BRAF mutation positive, a BRAF inhibitor drug with or without a MEK inhibitor drug that has also stopped working.

The approval of AMTAGVI is based on a study that measured response rate. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

Important Safety Information

What is the most important information that I should know about AMTAGVI?

You will likely be in a hospital prior to and after receiving AMTAGVI.

Before taking AMTAGVI, tell your healthcare provider about all of your medical conditions, including if you:

Have any lung, heart, liver or kidney problems
Have low blood pressure
Have a recent or active infection or other inflammatory conditions including cytomegalovirus (CMV) infection, hepatitis B or C or human immunodeficiency virus (HIV) infection
Are pregnant, think you may be pregnant, or plan to become pregnant
Are breastfeeding
Notice the symptoms of your cancer are getting worse
Have had a vaccination in the past 28 days or plan to have one in the next few months
Have been taking a blood thinner
Tell your doctor about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive AMTAGVI?

AMTAGVI is made from your surgically removed tumor. Tumor derived T cells are grown in a manufacturing center at the end of which they number in the billions of cells.
Your tumor tissue is sent to a manufacturing center to make AMTAGVI. It takes about 34 days from the time your tumor tissue is received at the manufacturing center until AMTAGVI is available to be shipped back to your healthcare provider, but the time may vary. Your AMTAGVI will be provided in 1-4 patient-specific infusion bag(s) containing 100 mL to 125 mL of viable (alive) cells per bag.
After your AMTAGVI arrives at your treating institution, your healthcare provider will give you lymphodepleting chemotherapy to prepare your body.
Approximately 30 to 60 minutes before you are given AMTAGVI, you may be given other medicines including:
Medicines for an allergic reaction (anti-histamines)
Medicines for fever (such as acetaminophen)
Your AMTAGVI will be provided in 1 to 4 infusion bag(s) containing 100 mL to 125 mL of viable cells per bag. When your body is ready for AMTAGVI infusion, your healthcare provider will give AMTAGVI to you by intravenous infusion. This usually takes less than 90 minutes.
After getting AMTAGVI

Beginning 3 to 24 hours after AMTAGVI is given, you may be given up to 6 doses of IL-2 (aldesleukin) every 8 to 12 hours via intravenous infusion. Your doctor may discontinue IL-2 (aldesleukin) infusion any time if you have severe side effects.

You will have to stay in the hospital until you have completed the IL-2 (aldesleukin) treatment and you have recovered from any serious side effects associated with the AMTAGVI treatment.

You should plan to stay within 2 hours of the location where you received your treatment for several weeks after getting AMTAGVI. Your healthcare provider will check to see if your treatment is working and help you with any side effects that occur.

What are the possible side effects of AMTAGVI?

The most common side effects of the AMTAGVI treatment include chills, fever, low white blood cell count (may increase risk of infections), fatigue, low red blood cell count (may cause you to feel tired or weak), fast or irregular heartbeat, rash, low blood pressure, and diarrhea.

These are not all the possible side effects of the AMTAGVI treatment. Talk with your healthcare provider for more information about AMTAGVI. You can ask your healthcare provider for information about AMTAGVI that is written for healthcare professionals.

You may report side effects to Iovance at 1-833-400-4682, or to the FDA, at 1-800-FDA-1088 or at www.fda.gov/medwatch.

Please see Full Prescribing Information and Patient Information, including Boxed Warning, for additional Important Safety Information.

On June 2, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta (γδ) T cell therapies for cancer and autoimmune diseases, reported new long-term clinical data from its fully enrolled Phase 1 trial of INB-200 in patients with newly diagnosed glioblastoma multiforme (GBM) (Press release, In8bio, JUN 2, 2025, View Source [SID1234653611]). The data were presented in an oral session on May 30th at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"Half of the patients who received multiple doses remained progression free for greater than a year and a half, demonstrating functional recoveries, with several patients also having the ability to return to work. No new relapses have been reported since the last clinical update in October 2024" stated Burt Nabors, M.D., Division Director, Neuro-Oncology at the Heersink School of Medicine at the University of Alabama at Birmingham and Principal Investigator of the study. "These early data highlight the potential of repeated intracranial dosing of IN8bio’s gamma-delta T cells to extend mPFS in GBM, including in patients with chemotherapy-resistant tumors."

The Phase 1 results of INB-200 demonstrate that repeated dosing of IN8bio’s proprietary Drug Resistant Immunotherapy (DRI) – which utilizes genetically modified gamma-delta T cells delivered directly into the brain – in combination with SOC maintenance chemotherapy (temozolomide), led to an mPFS of 16.1 months. This represents an improvement of more than double (+9.2 months or +132.6%) the historical mPFS of 6.9 months under the SOC Stupp protocol. These mPFS results have already surpassed the historical mOS of 14.6 months associated with the SOC Stupp protocol alone. By comparison, a 2 to 3 month improvement in mPFS has historically been considered as clinically significant and the bar for approval by the Food and Drug Administration (FDA).

Importantly, no dose-limiting toxicities (DLTs), CRS, or ICANS have been observed among patients treated with INB-200 (n=13). The majority of adverse events were Grade 1-2 and consistent with those typically associated with radiation and temozolomide. No treatment-related deaths have occurred.

Highlights from the Clinical Data as of May 31, 2025:

INB-200

Four patients (40%) who received repeated doses of INB-200 remain alive and progression free for a median of over two years, with three returning to work
No additional relapses were observed since the last data update on October 18, 2024
Among patients who received multiple doses of INB-200, mPFS reached 16.1 months, compared to 6.9 months with SOC and 8.3 months for patients who received only a single dose of INB-200
Repeat dosing demonstrated no additional safety risks, with most side effects being mild and attributable to the SOC therapy
50% of patients receiving repeated doses remained progression-free >18 months versus 0% of patients who received a single dose

INB-400

Data from our Phase 2 clinical trial of INB-400 in patients with newly diagnosed GBM, including three additional clinical sites, also show encouraging preliminary results: current mPFS is at 10.8 months. Additional updates expected late 2025

"Our goal is to achieve deeper responses and eliminate more cancer cells to ultimately extend the time patients can remain progression free and alive," stated William Ho, CEO and cofounder of IN8bio. "The data presented at ASCO (Free ASCO Whitepaper) by Dr. Nabors speaks to the potential of IN8bio’s gamma-delta T cells to provide a game-changing immunotherapy for this dire and life-threatening cancer. We believe that INB-200 represents a novel direction in therapy for the treatment of solid tumor cancers like GBM. The complete data from our Phase 1 trial and supporting data from our Phase 2 trial represent the first time a gamma-delta T cell therapy has shown the potential to extend mPFS beyond historical benchmarks."

IN8bio’s approach delivers gamma-delta T cells directly to the tumor cavity after surgery, applying sustained immune pressure to eliminate residual cancer cells. The Company’s DRI technology is designed to treat newly diagnosed GBM by harnessing the natural tumor-targeting power of gamma-delta T cells and the sensitizing effects of chemotherapy. This approach aims to eliminate the chemo-resistant cancer and stem cells that often survive SOC treatment and can lead to relapse.

Conference Call Details

IN8bio will host a conference call and webcast featuring Dr. Burt Nabors, the Principal Investigator, today, Monday, June 2, 2025 at 8:30 am EDT to review the updated clinical data from the ASCO (Free ASCO Whitepaper) presentation. The webcast can be accessed by clicking this link and can also be accessed on the Events & Presentations page of the Company’s website. To participate in the live call, please register using this link. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will be informed of the dial-in number and will be provided a unique PIN.

(1) Historical reported mPFS and mOS from Stupp Protocol (surgery, radiotherapy plus maintenance temozolomide); doi: 10.1056/NEJMoa043330

On June 2, 2025 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported that management will participate in the 2025 Jefferies Global Healthcare Conference (Press release, Immunocore, JUN 2, 2025, View Source [SID1234653610]).

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2025 Jefferies Global Healthcare Conference
Fireside Chat: Thursday, June 5, 2025, at 11:05 a.m. EDT

The presentation will be webcast live and can be accessed by visiting ‘Events & Presentations’, under ‘Events’, via the ‘Investors’ section of Immunocore’s website at www.immunocore.com. Following the event, a replay of the presentation will be made available for a limited time.

On June 2, 2025 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported that the U.S. Food and Drug Administration (FDA) has granted Expanded Access authorization for the use of its Cancer BioShield platform, anchored by ANKTIVA (nogapendekin alfa inbakicept-pmln), to treat lymphopenia in adult patients with refractory or relapsed solid tumors independent of tumor type who have progressed after first-line standard-of-care treatment, chemotherapy, radiation, or immunotherapy (Press release, ImmunityBio, JUN 2, 2025, View Source [SID1234653609]).

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To date no treatment exists for lymphopenia, a depletion of critical lymphocytes responsible for immunogenic cell death, specifically natural killer (NK) cells, killer CD8+ T cells and CD4+ with memory T cells. Treatment induced lymphopenia is a debilitating consequence of chemotherapy, radiation, and certain immunotherapies and steroids. This treatment-acquired immunodeficiency not only increases susceptibility to infections but also deprives the body’s immune system to fight residual or recurrent cancer, accelerating metastasis and disease progression, and contributing to early mortality. Countless publications over the last two decades has reported lymphopenia as a highly predictive biomarker of poor prognosis across all tumor types.1-6 Despite its significant clinical impact, the pharmaceutical industry has largely overlooked lymphopenia as a disease in its own right, and no approved therapies have existed to directly address it, until the approval of ANKTIVA in the treatment of BCG-unresponsive bladder cancer with the mechanism of action of an IL-15 superagonist proliferating key lymphocytes.7

While oncologists and patients have long had therapies such as EPOGEN and NEUPOGEN to manage chemotherapy- and radiation-induced anemia and neutropenia, no comparable option has been available for lymphopenia. ANKTIVA, an interleukin-15 (IL-15) agonist, is the first approved therapy with a defined mechanism of action to restore lymphocyte levels. It activates and proliferates NK and T cells without inducing immunosuppressive regulatory T cells (Tregs), offering the first solution for reversing this critical immune deficit of lymphocytes in cancer patients.7

"Lymphopenia has long been recognized as a major driver and predictor of early mortality in cancer—yet until now, it has remained unaddressed," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "This FDA authorization allows all patients with solid tumors suffering from immune collapse following first-line therapy of chemo, radiation, or immunotherapy to access ANKTIVA. The survival benefit we observed at ASCO (Free ASCO Whitepaper) 2025 in 3rd to 6th line advanced metastatic pancreatic cancer confirms that restoring lymphocyte levels—rather than depleting them—can change the course of disease."

At the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting, ImmunityBio presented landmark results showing that reversing lymphopenia with ANKTIVA and CAR-NK therapy significantly prolonged median overall survival in third- to sixth-line metastatic pancreatic cancer patients. This benefit was further enhanced when treatment began at lower tumor burdens, as indicated by CA19-9 levels. Highlighting the importance of lymphopenia reversal, Oncologist published a peer-reviewed paper titled "Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate," demonstrating that the patient with 2nd line metastatic pancreatic cancer treated with the full Cancer BioShield platform—including ANKTIVA, CAR-NK cells (PD-L1 t-haNK), and antigen-targeting adenoviruses—has remained in remission for over six years and maintains a high quality of life at the date of this release.

"We are entering a new era in oncology where the goal is not only to target the tumor but to protect and empower the immune system itself," continued Dr. Soon-Shiong. "Through this Expanded Access Program, we can now offer hope to patients with solid tumors who have exhausted standard options. Our mission is to transform cancer care by reversing the immune collapse that often leads to progression and mortality by enabling the body to serve as a factory for the regeneration and reconstitution of the lymphocytes key to immunogenic cell death of the tumor. By mitigating treatment induced lymphopenia from our standards of care, ANKTIVA can serve as a Cancer Bioshield."

In February 2025, ImmunityBio announced it had received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for ANKTIVA and CAR-NK (PD-L1 t-haNK) for the reversal of lymphopenia in patients receiving standard-of-care chemotherapy/radiotherapy and in relapsed locally advanced or metastatic pancreatic cancer. The RMAT designation is intended to expedite the development of therapies targeting serious or life-threatening conditions with unmet medical need.

Full results of our 2025 ASCO (Free ASCO Whitepaper) Annual Meeting can be found below:

Association of lymphopenia rescue and CA19-9 levels with overall survival following IL-15 superagonist N-803 and PD-L1 t-haNK chemo-immunotherapy for 3rd line or greater metastatic pancreatic cancer.
Abstract Text: View Source
Poster PDF: View Source

QUILT 3.076 phase 1 study of memory-like cytokine-enriched natural killer (M-CENK) cells plus N-803 in locally advanced or metastatic solid tumors.
Abstract Text: View Source
Poster PDF: View Source

About the Cancer BioShield Platform

The Cancer BioShield platform is a first-in-class immunotherapy strategy designed to restore immune competence by reversing lymphopenia—the loss of functional immune cells caused by cancer itself and by conventional treatments such as chemotherapy, radiation and immunotherapy. At its core is ANKTIVA (nogapendekin alfa inbakicept-pmln), an IL-15 agonist approved for BCG-unresponsive non–muscle-invasive bladder cancer CIS with or without papillary disease, activates and proliferates natural killer (NK) cells and CD4+ and CD8+ T cells, restoring lymphocyte levels critical for immunosurveillance, immunogenic cell death, and long-term tumor control.

The platform employs a multi-modal approach:

In-vivo stimulation: Subcutaneous administration of ANKTIVA expands NK and T cells, boosting anti-tumor immunity.
Ex-vivo targeted cytotoxicity: Off-the-shelf PD-L1 t-haNK CAR-NK cells are engineered to target and eliminate PD-L1–expressing tumor cells and immunosuppressive neutrophils (myeloid-derived suppressor cells), enhancing anti-tumor specificity and reducing immune evasion.
Memory Cytokine-Enriched Natural Killer (M-ceNK) cell therapy: M-ceNK cells are developed via cytokine activation and expansion of autologous and allogeneic NK cells collected through apheresis, potentially providing long-term immune memory and sustained cytotoxic capacity.
Together, these components offer a comprehensive, novel, immune-restoring therapeutic platform aimed at not only expanding effector immune cells, but also overcoming tumor-mediated immune suppression to support long-term disease control.

The platform’s effectiveness can be tracked through universally utilized simple complete blood count (CBC): increases in absolute lymphocyte count (ALC) reflect ANKTIVA’s lymphocyte-stimulating activity, while reductions in the neutrophil-to-lymphocyte ratio (NLR) demonstrate PD-L1 t-haNK’s immunosuppressive neutrophil targeting. Low ALC and high NLR levels6 are laboratory measurements that have been extensively reported as predictive biomarkers of poor prognosis with early mortality across all tumor types.1-6 The data presented by ImmunityBio for the first time demonstrates that improving ALC and NLR correlates with significant enhanced overall survival and clinical benefit.

With potential applications extending beyond oncology—including infectious disease, sepsis, and immune senescence—the Cancer BioShield Platform represents a potentially transformative shift in treating not just the tumor, but the underlying immune collapse that allows disease to progress.

About Lymphopenia and Absolute Lymphocyte Count (ALC)

Lymphopenia—the loss of key immune cells such as NK, CD4+, and CD8+ T cells—is a common side effect of chemotherapy1, radiation2,3, and some immunotherapies4. Unlike anemia and neutropenia, which have FDA-approved treatments like EPOGEN and NEUPOGEN, no therapy previously existed to treat this immune cell depletion. Lymphopenia weakens the immune system, increases infection risk, and is linked to early death across many cancer types.1-6 Low Absolute Lymphocyte Count (ALC) is a recognized poor prognostic marker. ANKTIVA is the first approved therapy to restore lymphocyte levels by activating and expanding NK and T cells—without increasing immunosuppressive T regulatory cells.

On June 2, 2025 Ichnos Glenmark Innovation (IGI), a global, fully integrated clinical-stage biotechnology company focused on developing multispecificsTM in oncology, reported promising full dose-escalation results from its Phase 1 TRIgnite-1 study of ISB 2001, an investigational first-in-class BCMA × CD38 × CD3-targeting trispecific antibody for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Ichnos Sciences, JUN 2, 2025, View Source;utm_medium=rss&utm_campaign=igi-asco-isb2001-high-orr-favorable-safety-data [SID1234653608]). These data, presented as a rapid oral presentation (Abstract #7514) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting, demonstrated a sustained overall response rate (ORR) of 79% and a high complete/stringent complete response (CR/sCR) rate of 30% across seven active dose levels (≥ 50 µg/kg) in a heavily pretreated patient population, with a favorable safety profile. The ORR was 74% in all treated patients, including two patients treated at lower dose levels.

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ISB 2001 was designed to simultaneously target multiple myeloma by binding to the tumor-associated antigens BCMA and CD38, even when expressed at low levels, while engaging T cells to trigger an immune response. This novel trispecific design enhances tumor-specific cytotoxicity and aims to overcome resistance mechanisms seen with first-generation bispecific antibodies and CAR T-cell therapies, while minimizing off-tumor toxicity.

Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St. Vincent’s Hospital Melbourne, said "Responses to ISB 2001 highlight the remarkable anti-myeloma activity of this first-in-class anti-BCMA × CD38 × CD3 trispecific antibody-T cell engager in heavily pretreated RRMM patients, including those who have exhausted prior T cell-redirecting, BCMA-targeted, or anti-CD38 therapies – an especially challenging, quad-exposed patient population. With its unprecedented potency and tolerability, ISB 2001 has the potential to redefine the treatment landscape for RRMM, offering new hope for patients with limited therapeutic options."

A total of 35 patients with at least one month of follow-up had received a median of six prior lines of therapy (range: 3–11) at study entry, underscoring a heavily pretreated population. ISB 2001 demonstrated high response rates at active dose levels, with 33 patients treated at ≥ 50 µg/kg (dose levels 3–9). Responses were durable and deepened over time, irrespective of prior lines of therapy or refractoriness status, reinforcing the strength of earlier findings reported at ASH (Free ASH Whitepaper) 2024 Annual Meeting in 18 patients treated with ISB 2001 at doses ≥ 50 µg/kg:

The ORR was 79% (26/33), including a CR/sCR rate of 30% (10/33), with a median follow-up of 6.3 months (range: 1–16).
Of the 10 patients achieving CR/sCR, eight were evaluable for minimal residual disease (MRD), and six achieved MRD negativity, indicating no detection of myeloma cells by molecular or flow cytometry assays with 10-5 sensitivity, and reinforcing the depth of response.
Among 25 patients refractory to anti-CD38 therapies, the ORR was 72%, with a CR/sCR rate of 24%.
In 19 patients without prior T-cell directed therapy (TCDT), including bispecific antibodies and/or CAR T-cell therapy, the ORR was 84%, with CR/sCR rate of 32%.
Among 14 patients previously treated with TCDT, the ORR remained strong at 71% with a CR/sCR rate of 28%.
In 15 patients who had received prior BCMA-targeted therapies, the ORR was 73%, with a CR/sCR rate of 27%.
The median half-life of ISB 2001 was approximately 17 days, supporting the potential for less-frequent dosing.
ISB 2001 demonstrated a favorable safety profile throughout the dose-escalation phase, with no dose-limiting toxicities (DLTs) reported. Cytokine release syndrome (CRS) occurred in 24 patients (69%), primarily Grade 1, with only four patients experiencing Grade 2 events. CRS was mostly limited to the first administration of ISB 2001, and no severe or life-threatening cases were observed. Drug-related severe infections were infrequent (4 patients, 11%), with no Grade 4 or higher infection. One patient experienced Grade 1 ICANS; no other drug-related neurologic adverse events were reported.

The dose-expansion portion of the Phase 1 study is ongoing to establish the recommended Phase 2 dose (RP2D) and the best dosing schedule to enable the first registrational study with ISB 2001.

"The high response rates and low safety concerns demonstrated in the dose-escalation portion of the TRIgnite-1 study, conducted in a heavily pretreated population across multiple types of therapies, reinforce the promise of ISB 2001 as a potential new treatment for patients," said Lida Pacaud, M.D., Chief Medical Officer at IGI. "As we advance to the second part of the TRIgnite-1 study, our focus is now on defining the recommended dosing schedule and evaluating ISB 2001 in a larger population of heavily pretreated RRMM patients, where we hope to observe similarly impressive treatment responses and tolerability."

About TRIgnite-1

TRIgnite-1 (NCT05862012) is an ongoing Phase 1, first-in-human, open-label, multicenter study evaluating the safety and anti-myeloma activity of ISB 2001 in patients with RRMM. The dose-escalation study enrolled patients with RRMM who were treated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies and are refractory to, or intolerant of, established therapies known to provide clinical benefit in multiple myeloma. Patients with prior CAR-T cell therapies, bispecifics and/or prior BCMA targeted agents were eligible.

The TRIgnite-1 study has two parts: dose escalation and dose expansion. The dataset presented comes from patients treated in the entire dose-escalation portion who have at least 1-month follow-up at six sites in the United States and Australia. The dose-expansion study is randomized, compliant with Project Optimus at the U.S. Food and Drug Administration (FDA), and is underway in the U.S. and Australia, with European enrollment beginning soon.

About ISB 2001 and Relapsed/Refractory Multiple Myeloma

ISB 2001 is a first-in-class trispecific T-cell engager that targets BCMA and CD38 on myeloma cells and CD3 on T cells. Developed using IGI’s proprietary BEAT protein platform, ISB 2001 was engineered with two distinct binders against myeloma-associated antigens to enhance avidity, even at low target expression levels, while aiming to improve safety over first-generation bispecific antibodies.

The U.S. Food and Drug Administration (FDA) granted ISB 2001 Fast Track Designation in May 2025 and Orphan Drug Designation in July 2023.

Nearly all patients with RRMM ultimately experience disease progression. With no cure currently available and limited treatment options once approved therapies are exhausted, there remains a significant unmet need. IGI is developing ISB 2001 to address this gap, specifically for patients who have previously received T-cell–directed therapies, including CAR T-cell treatments and bispecific antibodies.