On June 3, 2023 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral (IT) cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from its ongoing phase 1/2 clinical trial demonstrating the efficacy and tolerability of INT230-6, either as monotherapy or in combination with ipilimumab in patients with relapsed, refractory and metastatic sarcomas, will be presented this afternoon at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago and virtually from June 2-6, 2023 (Press release, Intensity Therapeutics, JUN 3, 2023, View Source [SID1234632422]).

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Abstract Title: Intratumoral INT230-6 (Cisplatin, Vinblastine, SHAO) alone or with ipilimumab (IPI) prolonged survival with favorable safety in adults with refractory sarcomas [Intensity IT-01; BMS#CA184-592].
Presenter/First Author: Christian F. Meyer, MD, Johns Hopkins Sydney Kimmel Cancer Center
Session Title: Sarcoma
Poster Session Date and Time: Saturday, June 3, 2023, 1:15 PM – 4:15 PM EDT
Location: Exhibit Hall
Abstract Number: 11568
Poster number: 502

Copies of the presentation materials are available on Intensity’s website on the publications, papers and posters page.

Sarcoma remains a very challenging cancer to treat and has historically proven resistant to checkpoint blockade. Novel approaches are needed for this patient population, and Intensity’s data indicate that sarcoma is an attractive target for intratumoral injection. Christian Frederick Meyer, M.D., Ph.D., M.S. Assistant Professor of Oncology at the Sidney Kimmel Cancer Center at Johns Hopkins University is an investigator for Intensity’s phase 1/2 clinical trial and the presenter of the data at ASCO (Free ASCO Whitepaper). Dr. Meyer has placed a number of his sarcoma patients into the study. INT230-6 has demonstrated significant survival prolongation and continues to be of great interest to a sarcoma oncologists, such as Dr. Meyer, especially given the data on immune ignition, as sarcoma is considered non-immunogenic and therefore largely unresponsive to immunotherapies.

"The prolonged survival of nearly 450 days compared to what would be expected in such a severe sarcoma patient population is a testament to the strength of our novel drug’s potency," stated Lewis H. Bender, President and Chief Executive Officer of Intensity. "Causing significant tumor necrosis, immune infiltrates, uninjected tumor shrinkage and prolonged survival provides strong proof-of-concept evidence of our drug’s mechanism of action and underscores the potential of INT230-6 to help metastatic sarcoma patients. As recent data readouts demonstrate, there remains a high unmet need for new therapeutic approaches to treat metastatic cancers in general. With that in mind, we have discussed our next steps with the U.S. Food and Drug Administration, drafted a protocol and look forward to advancing INT230-6 into a phase 3 trial for sarcoma patients."

Efficacy in subjects administered INT230-6, with or without ipilimumab, were compared to a synthetic control. The poster reports the median overall survival (mOS) and disease control rate (DCR equals the cases of stable disease, partial response and complete response divided by number of subjects) per the Response Evaluation Criteria in Solid Tumors (RECIST). Abscopal responses for INT230-6 alone were observed primarily in subjects dosed ≥ 40% of their total tumor burden (TTB). The DCR for the all-treated population (those who received at least one dose of INT230-6) was 93% for monotherapy and 86% for the ipilimumab combination. For the combination arm, one subject had yet to reach the first timepoint for SD at the time of data cut-off.

Study IT-01 was without a randomized control group; however, published clinical phase 1/2 basket trials in sarcoma report mOS ranging from 7.6 to 9.6 months (Jones et. al., Cancer Chemotherapy Pharmacology (2011) 68:423–429; Cassier et. al., Annals of Oncology 25: 1222–1228, 201; vi. Subbiah et. al., Scientific Reports | 6:35448 2016). Using the Subbiah study data and the Royal Marsden Hospital scoring system to predict survival for the sarcoma subjects from the IT-01 study, a synthetic Kaplan Meier (KM) control curve was generated. The overall survival of the control, all INT230-6 patients in sarcoma, including those receiving a cumulative dose of greater than 40% of their TTB, are shown in the below table.

Phase 1/2 studies Control (Subbiah) INT230-6 all INT230-6 >40% TTB INT230-6 + IPI
Median OS 205 days 649 days Not yet reached Not yet reached
Confidence Interval – (146, NR)
Sample size 56 15 11 14

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

On June 3, 2023 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious diseases and autoimmune conditions, reported two posters at the 2023 American Society for Clinical Oncology meeting (Press release, Immunocore, JUN 3, 2023, View Source [SID1234632420]):

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A poster including an analysis of circulating tumor DNA (ctDNA) data from the Phase 3 KIMMTRAK (tebentafusp-tebn) trial in HLA-A*02:01 patients with metastatic uveal melanoma (mUM)
A trial-in-progress poster describing the design of the Phase 2/3 trial with tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01 patients with previously treated advanced melanoma.
"We have shown that KIMMTRAK can deliver significant OS benefit to patients with metastatic uveal melanoma, regardless of best RECIST response. We have now validated ctDNA reduction as an early surrogate for OS in two separate clinical trials," said Koustubh Ranade, Vice President of Translational Medicine at Immunocore. "ctDNA reduction is one of the dual endpoints in our ongoing Phase 2/3 trial with tebentafusp in patients with previously treated advanced or metastatic melanoma."

In this analysis of the Phase 3 data for patients with best response of stable disease treated with KIMMTRAK, ctDNA reduction by week 9 was observed in 94% of patients (34/36) with detectable ctDNA at baseline, and this reduction was associated with longer overall survival (OS). These data were consistent with those presented at AACR (Free AACR Whitepaper) 2023 in showing that ctDNA reduction by week 9 was strongly associated with improved OS, even in patients with best RECIST response of progressive disease – further indicating that RECIST responses underestimate tebentafusp’s clinical benefits, and that early reduction in ctDNA may be a better predictor of long OS than radiographic response.

The Company also presented a trial-in-progress poster for the Phase 2/3 trial that has started randomizing patients with previously treated advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients will be randomized to one of three arms including tebentafusp, as monotherapy or in combination with an anti-PD1, and a control arm.

Poster details

Title: Early ctDNA reduction may identify patients with stable disease and long OS on tebentafusp
Presenting author: Dan Feng
Session: Melanoma/Skin cancers

Title: A Phase 2/3 trial in progress on tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01+ patients with previously treated advanced, non-uveal melanoma
Presenting author: Diwakar Davar
Session: Melanoma/Skin cancers (Trial in Progress)

##

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

About Phase 3 IMCgp100-202 Trial
IMCgp100-202 (NCT03070392) is a randomized pivotal trial that evaluated overall survival (OS) of KIMMTRAK compared to investigator’s choice (either pembrolizumab, ipilimumab, or dacarbazine) in HLA-A*02:01-positive adult patients with previously untreated mUM. KIMMTRAK demonstrated an unprecedented OS benefit with a Hazard Ratio (HR) in the intent-to-treat population favoring KIMMTRAK, HR=0.51 (95% CI: 0.37, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine).

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity
KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

On June 3, 2023 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, together with CSPC Pharmaceutical Group Limited (CSPC; HKEX: 01093), reported promising initial clinical data for SYSA1801 (EO-3021) from the ongoing Phase 1 dose escalation and expansion study in China (Press release, Elevation Oncology, JUN 3, 2023, View Source;utm_medium=rss&utm_campaign=elevation-oncology-highlights-first-in-human-phase-1-sysa1801-eo-3021-clinical-data-to-be-presented-by-partner-cspc-pharmaceutical-group-limited-at-asco-2023 [SID1234632418]). These data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting, being held June 2-6, 2023, in Chicago, IL.

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EO-3021 is a potential best-in-class antibody-drug conjugate (ADC) that has been designed to selectively deliver a cytotoxic payload directly to Claudin 18.2-expressing cancer cells to minimize toxicities and maximize anti-tumor activity. EO-3021 is a fully human monoclonal antibody (mAb) that targets Claudin 18.2 and is site-specifically conjugated to the cytotoxic agent monomethyl auristatin E (MMAE), via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Elevation Oncology’s partner, CSPC, is actively recruiting patients in the Phase 1 clinical trial of SYSA1801 (EO-3021) in China (NCT05009966).

"In these preliminary Phase 1 data, EO-3021 demonstrated an objective response rate of 47% in patients with resistant/refractory gastric cancer expressing Claudin 18.2, with a well-tolerated safety profile in a heavily pretreated patient population," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "While the study remains ongoing, the responses seen are particularly impressive, especially in the gastric cancer setting in tumors expressing Claudin 18.2. These results are highly informative as Elevation Oncology prepares to initiate a Phase 1 clinical trial of EO-3021 in the US in the second half of 2023."

"We are highly encouraged by these Phase 1 study data which demonstrate that SYSA1801 (EO-3021) is an active drug that has a well-tolerated safety profile in patients with difficult to treat cancers," said Chunlei Li, Ph.D., Chief Scientific Officer of CSPC Pharmaceutical Group Limited. "These data support the potential of this unique product candidate for patients with Claudin 18.2-expressing cancers."

Key Findings from the Phase 1 Study

As of the data cutoff date of November 5, 2022, 33 patients with resistant/refractory solid tumors that expressed Claudin 18.2 were enrolled
Patients received 0.5 mg/kg to 3 mg/kg of SYSA1801 (EO-3021) administered intravenously (IV) every 3 weeks (Q3W) as part of the dose escalation (n=17) portion of the study; in the dose expansion portion of the study, patients (n=16) were treated at effective doses (2.0 mg/kg IV Q3W and 2.5 mg/kg IV Q3W)
26 patients (78.8%) had gastric cancer (GC); 7 patients (21.2%) had pancreatic cancer
11 patients (33.3%) had been pretreated with ≥3 prior lines of therapy
21 patients (gastric cancer n=17; pancreatic cancer n=4) were evaluable for efficacy per RECIST v1.1
In gastric cancer, the objective response rate (ORR) was 47.1% (8 PRs, including 4 confirmed PRs) and the disease control rate (DCR) was 64.7%, including three patients with stable disease (SD)
The overall ORR was 38.1% (8 PRs, including 4 confirmed PRs) and DCR was 57.1% (including 4 SDs)
Of the 33 patients enrolled at the time of data cutoff, treatment-related adverse events (TRAEs) of any grade occurred in 25 patients (75.8%), including eight (24.2%) TRAEs of ≥Grade 3
The most common TRAEs (occurring in >20% of patients) were nausea (42.4%), vomiting (36.4%), dry eye syndrome (21.2%) and anemia (21.2%)
Two dose-limiting toxicities (DLTs) of Grade 3 nausea and vomiting occurred at the 3 mg/kg IV Q3W dose
No treatment-related deaths were reported
The dose escalation and expansion portion of the study in China is ongoing
Details for the ASCO (Free ASCO Whitepaper) 2023 Presentation are as Follows:

Title: First-in-human dose escalation and expansion study of SYSA1801, an antibody-drug conjugate targeting claudin 18.2 in patients with resistant/refractory solid tumors.
Presenter: Dr. Yakun Wang
Session Type: Poster Discussion Session
Session Title: Molecularly Targeted Agents and Tumor Biology
Poster Session Date and Time: Saturday, June 3, 2023, 8:00 a.m. – 11:00 a.m. CT
Poster Discussion Date and Time: Saturday, June 3, 2023, at 1:15 p.m. CT
Abstract Number: 3016
Poster Number: 214

The full presentation can be accessed under the resources and publications page of the Elevation Oncology website following the completion of the presentation session at ASCO (Free ASCO Whitepaper).

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation in many solid tumors, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. An Investigational New Drug application for EO-3021 has been cleared by the U.S. Food and Drug Administration.

On June 3, 2023 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive lead-in data from its ongoing Phase 3 PEAK trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with Gastrointestinal Stromal Tumors (GIST) (Press release, Cogent Biosciences, JUN 3, 2023, View Source [SID1234632417]). The data are being presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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"The results presented today from the lead-in portion of the PEAK study are very encouraging, as the data continue to show that the combination of bezuclastinib and sunitinib has impressive clinical activity in highly refractory GIST patients and is well-tolerated," said Andrew Wagner, M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. "These data reinforce the importance of the ongoing Phase 3 PEAK clinical trial, which has the potential to bring a new standard of care to imatinib-resistant GIST patients."

"These data reinforce our belief that the combination of bezuclastinib and sunitinib has the potential to become a new treatment option for second-line GIST patients," said Andrew Robbins, President, and Chief Executive Officer at Cogent Biosciences. "We are pleased to demonstrate in a robust clinical dataset that the addition of bezuclastinib to sunitinib does not appear to change the frequency or severity of adverse events associated with sunitinib monotherapy. In addition, we are encouraged by the performance of this combination in second-line GIST patients, the population we are currently enrolling in the Phase 3 PEAK clinical trial, with a disease control rate of 100% and 4 out of 7 patients now on treatment for more than 10 cycles."

PEAK Study Design
The PEAK study is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib in GIST patients previously treated with imatinib. As of the data cutoff date of March 29, 2023, 39 patients had been treated in Part 1, with 19 patients in Part 1a and 20 patients in Part 1b. Seven patients had received only imatinib as prior therapy, and 32 patients had received at least 2 prior tyrosine kinase inhibitor (TKI) therapies.

Safety Data
As of the cutoff date of March 29, 2023, the combination of bezuclastinib and sunitinib was generally well-tolerated with an encouraging safety profile. The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible, with a low rate of Grade 3 or higher events observed. 23% of patients experienced dose reductions of either medication, and only two patients discontinued treatment due to adverse events. Across Part 1a and Part 1b, there were only two patients with serious adverse events reported that were possibly associated with either study medication including one patient with grade 2 neutrophil count decrease and pyrexia and grade 3 platelet count decrease and one patient with grade 2 bacterial peritonitis and grade 3 febrile neutropenia. Overall, the safety and tolerability profile of the combination appears consistent with that of single-agent sunitinib, suggesting that bezuclastinib is not adding to the overall frequency or severity of adverse events associated with single-agent sunitinib.

Clinical Activity Data
As of the cutoff date, 39 patients had been treated for at least one 28-day cycle, with a range of 1-13 cycles, and 25 of the 39 patients continue to receive treatment. Data were immature to estimate median progression free survival. Across the efficacy evaluable patients in Part 1, the disease control rate (CR + PR + durable SD) is currently 55%; including a 100% disease control rate and 17% ORR among the efficacy evaluable 2nd-line patients in Part 1a. Across the study, 21 patients have demonstrated radiographic evidence of reduction in target lesion diameter, including 4 patients who have achieved partial response. Among those responders the time to first response was as long as 8 cycles, suggesting that patients currently early in treatment may achieve responses over time.

As of June 1, 2023 four of the seven 2nd-line patients in Part 1a remain on study with at least 10 cycles of therapy.

Bezuclastinib Clinical Development
Cogent is actively enrolling patients in Part 2 of the Phase 3 registration-enabling PEAK trial, which is expected to include approximately 388 second-line, post imatinib GIST patients. Additionally, Cogent remains on track to present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 trial of bezuclastinib in patients with nonadvanced systemic mastocytosis in the second half of 2023. Data will include safety/tolerability, pharmacokinetics, and measures of clinical activity. The Company also expects to present clinical data from approximately 30 patients in Part 1 of the Phase 2 APEX trial in patients with advanced systemic mastocytosis at a scientific meeting in the second half of 2023.

Webcast Information and ASCO (Free ASCO Whitepaper) Poster
Cogent will host a webcast on Monday, June 5, 2023 at 8:00 a.m. ET (7:00 a.m. CT) to discuss today’s update, with participation from Andrew Wagner, M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. The live event can be accessed on the Investor page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days.

The ASCO (Free ASCO Whitepaper) poster is available to registered conference attendees and is also in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research.

On June 3, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported long-term follow up data from the Phase 1 ALPHA/ALPHA2 trials of ALLO-501/501A in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Allogene, JUN 3, 2023, View Source [SID1234632413]). These data will also be presented in a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress on June 9, 2023.

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"We are excited to be the first to demonstrate the potential of allogeneic CD19 CAR T to induce durable complete remissions at a rate similar to approved autologous CD19 CAR T therapies. Our Phase 2 regimen also had a safety profile, including immune recovery, in line with approved options," said Zachary Roberts, M.D., Ph.D., Executive Vice President, Research & Development and Chief Medical Officer. "We believe our AlloCAR T product candidates have the potential to break down widespread access barriers to CAR T, and ultimately establish a new paradigm in cell therapy. These data underlie the excitement we and investigators have for our ongoing potentially pivotal Phase 2 ALPHA2 trial."

The updated analysis of ALPHA/ALPHA2 examined data from 12 CAR T-naïve patients with r/r LBCL who received a single dose of ALLO-501/501A manufactured using the Alloy process following a lymphodepletion regimen (FCA90) comprised of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) plus ALLO-647 (30 mg/day x 3 days). The median time from enrollment to the start of therapy was three days and all 12 patients were followed through a minimum of six months (data cutoff April 20, 2023).

Patients Treated with Phase 2 Regimen
(n=12)
Overall Response Rate (ORR), n (%) 8 (67)
Complete Response Rate (CR), n (%) 7 (58)
6 Month Complete Response, n (%) 5 (42)
As of the data cutoff, 7 of 12 (58%) patients achieved a CR and five (42%) maintained a CR through Month 6. Of the five patients who were in CR at 6 months, four (80%) remained in CR. The fifth patient had disease progression at 24 months. The median duration of response was 23.1 months with three patients remaining in remission for over 24 months and the longest remaining in remission for over 31 months.

All r/r CAR T naïve LBCL (N=33) Patients Treated with Phase 2 Regimen (N=12)
All Gr
N (%) Gr 3+
N (%) All Gr
N (%) Gr 3+
N (%)
CRS 8 (24) 0 4 (33) 0
ICANS 0 0 0 0
Neurotoxicity 13 (39) 2 (6) 4 (33) 0
GvHD 0 0 0 0
IRR 16 (49) 3 (9) 8 (67) 0
Infection 19 (58) 5 (15) 8 (67) 1 (8)
Prolonged Gr3+ Cytopenia - 4 (12) - 2 (17)
A safety analysis of 33 CAR T-naïve LBCL patients receiving Alloy process ALLO-501/501A product candidates at any dose and lymphodepletion schedule, including the 12 patients treated with the Phase 2 regimen, was also conducted. Treatment was generally well tolerated with no incidences of Grade 3 or greater cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome or graft versus host disease. Cytopenias and infections were manageable and comparable to the experience with autologous CAR T cell therapies in patients with r/r LBCL.

The ALPHA/ALPHA2 Phase 1 trials were designed to assess the safety, tolerability, and preliminary efficacy at increasing dose levels of ALLO-501 and ALLO-501A, allogeneic CAR T cell product candidates that target CD19. In addition to exploring cell doses, these studies evaluated various doses of ALLO-647, Allogene’s proprietary lymphodepleting antibody designed to prevent premature rejection of AlloCAR T cells. Allogene is currently enrolling the potentially pivotal Phase 2 ALPHA2 trial of ALLO-501A in LBCL and expects to complete enrollment in 1H2024.

About ALLO-501 and ALLO-501A
ALLO-501 and ALLO-501A are anti-CD19 AlloCAR T investigational products for the treatment of large B cell lymphoma. ALLO-501A, a next-generation anti-CD19 AlloCAR T, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. This product candidate is currently being studied in an ongoing potentially pivotal Phase 2 trial. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL.