On May 25, 2023 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported multiple presentations at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL from June 2-6, 2023 (Press release, Replimune, MAY 25, 2023, View Source [SID1234632075]).

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Replimune has one abstract selected for a poster discussion session that will include updated results from the first 75 patients treated with RP1 combined with nivolumab from the anti-PD1 failed melanoma cohort of the IGNYTE clinical trial. In addition, the Company will also present data from the Phase 1 trial of RP2 combined with nivolumab in uveal melanoma, and trial-in-progress posters from the RP2/3 programs.

Details for the presentations are as follows:

Data Presentations

Abstract Title: Initial efficacy and safety of RP1 + nivolumab in patients with anti–PD-1–failed melanoma from the ongoing phase 1/2 IGNYTE study

Poster Session Title: Melanoma/Skin Cancers
Poster Session Date and Time: Saturday, June 3, 2023, 1:15 PM-4:15 PM CDT
Poster Location: McCormick Place, Exhibit Hall A, Poster 272
Abstract: 9509
The IGNYTE poster will be discussed as part of a poster discussion session focused on melanoma/skin cancers on Saturday, June 3, 2023 at 4:30 pm CDT in S406 at McCormick Place.

Abstract Title: Preliminary safety and efficacy results from an open-label, multicenter, phase 1 study of RP2 as a single agent and in combination with nivolumab in a cohort of patients with uveal melanoma

Session Title: Melanoma/Skin Cancers
Session Date and Time: Saturday, June 3, 2023, 1:15 PM-4:15 PM CDT
Location: McCormick Place, Exhibit Hall A, Poster 290
Abstract: 9527
Trial-in-progress presentations

Abstract Title: A phase 2, open-label, multicenter study investigating efficacy and safety of RP3 oncolytic immunotherapy combined with other therapies in patients with locoregionally advanced or recurrent squamous cell carcinoma of the head and neck

Session Title: Head and Neck Cancer
Session Date and Time: Monday, June 5, 2023,1:15 PM-4:15 PM CDT
Location: McCormick Place, Exhibit Hall A, Poster 95b
Abstract: TPS6106
Abstract Title: An open-label clinical trial of RP2 and RP3 oncolytic immunotherapy in combination with atezolizumab and bevacizumab for the treatment of patients with advanced colorectal carcinoma

Session Title: Gastrointestinal Cancer—Colorectal and Anal
Session Date and Time: Monday, June 5, 2023, 8:00 AM-11:00 AM CDT
Location: McCormick Place, Exhibit Hall A, Poster 326a
Abstract: TPS3628
Abstract Title: An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma

Session Title: Gastroesophageal, Pancreatic, and Hepatobiliary
Session Date and Time: Monday, June 5, 2023, 8:00 AM-11:00 AM CDT
Location: McCormick Place, Exhibit Hall A, Poster 495b
Abstract: TPS4178
About IGNYTE
IGNYTE is Replimune’s multi-cohort Phase 1/2 trial of RP1 plus nivolumab. There are 3 tumor specific cohorts currently enrolling in this clinical trial including a 125-patient cohort in anti-PD1 failed melanoma with registrational intent. This cohort was initiated after completing enrollment in a prior Phase 2 cohort in the same clinical trial of approximately 30 patients with melanoma. The additional cohorts are in non-melanoma skin cancers which includes both naïve and anti-PD1 failed CSCC, and in anti-PD1 failed microsatellite instability high, or MSI-H/dMMR tumors. This trial is being conducted under a collaboration and supply agreement with Bristol-Myers Squibb.

About RP1
RP1 is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

About RP2 & RP3
RP2 and RP3 are derivatives of RP1 that express additional immune-activating proteins. RP2 expresses an anti-CTLA-4 antibody-like molecule and RP3 additionally expresses the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL, but does not express GM-CSF. RP2 and RP3 are intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity.

On May 25, 2023 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, reported complete first-in-human dose escalation data for RLY-4008, an investigational, potent, selective and oral small molecule inhibitor of fibroblast growth factor receptor 2 (FGFR2) (Press release, Relay Therapeutics, MAY 25, 2023, View Source [SID1234632074]). These data, from the global Phase 1/2 ReFocus study in patients with FGFR2-altered cholangiocarcinoma (CCA) and multiple other solid tumors, will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4, 2023. The data being presented at ASCO (Free ASCO Whitepaper) are generally consistent with those previously reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2022.

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Key Data to be Presented at 2023 ASCO (Free ASCO Whitepaper) Annual Meeting

The data that will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting are from the dose escalation portion of the ReFocus study, with a cut-off date of January 30, 2023. The dose escalation portion of the study enrolled 116 patients with advanced, FGFR2-altered solid tumors, the majority of whom have CCA (n=91), and investigated 15 doses, ranging from 20mg to 100mg, across three dose schedules – once daily (QD), once daily intermittent and twice daily.

The ongoing dose expansion portion of the study includes pivotal and pivotal-supportive cohorts in CCA patients as well as three tumor-agnostic cohorts in patients with other tumor types (non-CCA). Data from the three non-CCA dose expansion cohorts will be presented in the second half of 2023.

Among the 91 CCA patients in the dose escalation portion of the study, 25 had FGFR2 fusions and had not previously received an FGFR inhibitor (FGFRi-naïve FGFR2-fusion CCA). This represents a subset of the interim data reported at ESMO (Free ESMO Whitepaper) in September 2022, which also included some patients from the ongoing dose expansion cohorts.

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Eleven of these patients were treated at or above the pivotal dose of 70mg QD
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All 11 patients experienced radiographic tumor reductions
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Eight of the 11 patients (including all 4 patients receiving the pivotal dose) had a partial response (73% overall response rate (ORR)), and an additional three patients experienced a best response of stable disease
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The median duration of response (DoR) was 11.2 months
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Maximum treatment duration is from a patient who remains on treatment at 27 months as of the data cut-off date of January 30, 2023
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Fourteen patients were treated at doses below the 70mg QD pivotal dose

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Twelve of 14 patients experienced radiographic tumor reductions
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Five patients experienced a partial response (36% ORR), and six patients experienced a best response of stable disease
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Median DoR was 5.6 months
The dose escalation portion of the study also included 50 CCA patients with FGFR2 fusions who were previously treated with a non-selective FGFR inhibitor.

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In patients treated at or above the pivotal dose of 70mg QD (n=14), the ORR was 21 percent, and in patients treated at doses below the 70mg QD pivotal dose (n=36), the ORR was 11 percent
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Multiple partial responses occurred in patients with detected V565 and/or N550 mutations
In addition, across all doses, there were early signs of activity in the 14 CCA patients with FGFR2 mutations.

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Nine patients experienced radiographic tumor reductions and four patients experienced a partial response (29% ORR)
The safety analysis from the complete dose escalation portion of the study was generally consistent with the analysis from the 2022 ESMO (Free ESMO Whitepaper) data disclosure, which also included patients treated at the 70mg QD dose in the expansion cohorts:

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Most treatment-related adverse events were expected FGFR2 on-target, low-grade, monitorable, generally manageable and largely reversible
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There were no observed Grade 4 or 5 adverse events
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Off-target toxicities of hyperphosphatemia and diarrhea continued to be clinically insignificant
The ASCO (Free ASCO Whitepaper) presentation will be available on the Relay Therapeutics website under Publications: View Source after it is presented on June 4, 2023.

Key Upcoming RLY-4008 Milestones

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Complete enrollment of pivotal cohort (FGFRi-naïve FGFR2-fusion CCA patients) in the second half of 2023
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Initial data from non-CCA expansion cohorts in the second half of 2023
About RLY-4008

RLY-4008 is a potent, selective and oral small molecule inhibitor of FGFR2, a receptor tyrosine kinase that is frequently altered in certain cancers. FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. Preclinically, RLY-4008 demonstrated FGFR2-dependent killing in cancer cell lines and induced regression in in vivo models, while minimal inhibition of other targets was observed, including other members of the FGFR family. In addition, RLY-4008 demonstrated strong activity against known clinical on-target resistance mutations in cellular and in vivo preclinical models. RLY-4008 is currently being evaluated in ReFocus, a Phase 1/2 study in patients with advanced or metastatic FGFR2-altered solid tumors with a single arm, potentially registration-enabling cohort for FGFRi-naïve FGFR2-fusion CCA.

ReFocus Background

RLY-4008 is currently being evaluated in the global ReFocus Phase 1/2 study in patients with FGFR2-altered CCA and multiple other solid tumors, including a single arm, potentially registration-enabling cohort for FGFRi-naïve FGFR2-fusion CCA. The Phase 1 dose escalation portion of the study has been completed, and 70mg QD has been selected as the registrational dose. The expansion cohorts were initiated in December 2021 and now consist of seven different cohorts based on FGFR2 alteration and tumor type. Of the seven cohorts, the potential pivotal cohort consists of approximately 100 previously treated, FGFRi-naïve FGFR2-fusion CCA patients. To learn more about the ReFocus study, please visit here.

On May 25, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported updated data from two Phase 2 expansion dose cohorts evaluating investigational linvoseltamab (formerly REGN5458) in patients with heavily pre-treated, relapsed/refractory (R/R) multiple myeloma (Press release, Regeneron, MAY 25, 2023, View Source [SID1234632072]). The results will be shared in an oral session at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the LINKER-MM1 trial will form the basis of planned submissions to regulatory authorities, including to the U.S. Food and Drug Administration (FDA) later this year. Linvoseltamab is an investigational BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

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"Despite advances, new treatments are needed that drive meaningful and durable responses to help patients with relapsed and/or refractory multiple myeloma," said Hans Lee, M.D., Associate Professor and Director, Multiple Myeloma Clinical Research at The University of Texas MD Anderson Cancer Center. "Treatment with linvoseltamab at the recommended 200 mg dose in the LINKER-MM1 trial demonstrated impressive efficacy, with rapid, deep and durable responses in patients with multiple myeloma that’s highly refractory to standard therapies. Moreover, less than half of patients experienced any grade cytokine release syndrome, which was mostly Grade 1, with some Grade 2 and a single Grade 3 case. This reinforces the potential of linvoseltamab as a promising treatment option."

The new data to be presented at ASCO (Free ASCO Whitepaper) 2023 are from patients treated in the 50 mg (n=104) and 200 mg (n=117) cohorts of the Phase 1/2 trial. Initial results were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2022. Among the 200 mg cohort, the median soluble BCMA (sBCMA) was 377 ng/mL, 22% had bone marrow plasma cells ≥50% and 36% had high-risk cytogenetics, representing a patient population with a high disease burden and poor prognosis. The primary endpoint was objective response rate (ORR) assessed by independent review committee, which will be available when the data are more mature. The secondary endpoints included ORR and other efficacy measures assessed by local investigator. With a median follow-up of 6 months, patients receiving the recommended 200 mg dose showed:

71% ORR, per local investigator.
59% achieved a very good partial response (VGPR) or better, with 30% achieving a complete response (CR) or stringent complete response (sCR), per local investigator. Based on earlier results, responses may deepen with longer follow-up.
Median time to onset of response was less than 1 month.
84% and 79% probability of maintaining a response at 6 and 12 months, respectively, per Kaplan-Meier estimates.
Median progression-free survival was not reached.
Strong efficacy per ORR was consistently observed in the 200 mg cohort across multiple subgroups, even in high risk patients such as adults ≥75 years of age (n=31; 68%), patients with International Staging System (ISS) stage II and III disease (n=44 and 22; 73% and 59% respectively), patients with extramedullary plasmacytomas (defined as disease without bone association, n=16; 56%) as well as patients with baseline sBCMA ≥400 ng/mL (n=51; 55%). Additionally, among patients treated with 50 mg and 200 mg that achieved CR or sCR with available minimal residual disease (MRD) data, 54% were MRD negative at 10-5.

No new safety signals were identified with longer follow-up in the Phase 1 or Phase 2 portions of the trial. Among all patients in the 200 mg cohort, 79% experienced Grade ≥3 adverse events (AE). Most commonly occurring AEs (in ≥20% of patients) were cytokine release syndrome (CRS; 45%), neutropenia, cough, fatigue and diarrhea (33% each), anemia (27%), arthralgia (26%), and headache (23%). Discontinuations due to an AE occurred in 16% of patients. Deaths due to treatment-emergent AEs, on-treatment or within 30 days post last dose, in the 200 mg cohort were reported in 6 patients. None of the deaths were considered related to treatment per the treating physician. Among the 200 mg cohort, the majority of CRS cases were mild or moderate, there was a single case of Grade 3 CRS, and no cases of ≥Grade 4 CRS. The median time to first CRS onset was 15 hours (range: 0-177 hours), with the median time to resolution within 1 day (17 hours; range: 1-144 hours). Among the 50 mg and 200 mg dose cohorts (n=221), there were 14 immune effector cell-associated neurotoxicity syndrome events (ICANS, 6% all Grades; 2% Grades 3-4).

"With these latest pivotal results, linvoseltamab demonstrated notable response rates, providing encouraging evidence for this bispecific antibody," said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Hematology at Regeneron. "We designed linvoseltamab with patient needs at the center and are proud that it has provided benefit across the spectrum of relapsed refractory multiple myeloma patients, even those with hard-to-treat disease. We look forward to sharing these data with regulatory authorities with the goal of bringing this medicine to patients with heavily pre-treated multiple myeloma as soon as possible."

Based on these data, the Phase 3 development program investigating linvoseltamab in earlier stages of the disease has been initiated. In the U.S., linvoseltamab has been granted Fast Track Designation for multiple myeloma by the FDA. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

About the Phase 1/2 Trial
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion trial is investigating linvoseltamab in patients with R/R multiple myeloma. Among the 282 patients enrolled, all have received at least three prior lines of therapy or are triple refractory. Patients were administered linvoseltamab utilizing a step-up dosing regimen that was designed to help mitigate CRS.

The Phase 1 dose-escalation portion of the trial, which is now complete, primarily assessed safety, tolerability and dose-limiting toxicities across 9 dose levels of linvoseltamab exploring different administration regimens. The fully-enrolled Phase 2 dose expansion portion of the trial is further assessing the safety and anti-tumor activity of linvoseltamab, with a primary objective of ORR. Key secondary objectives include duration of response, progression free survival, rate of minimal residual disease negative status and overall survival.

About Multiple Myeloma
Multiple myeloma is the second most common blood cancer. Globally, there were 176,404 new diagnoses in 2020 and 35,730 new diagnoses estimated for 2023 in the U.S. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Multiple myeloma is not curable despite treatment advances, and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies. In addition, patients are at increased risk of frequent infections, bone fracture and pain, reduced kidney function, and anemia.

On May 25, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive data from three independent cohorts evaluating an investigational combination of LAG-3 inhibitor fianlimab and PD-1 inhibitor Libtayo (cemiplimab) in adults with advanced melanoma (Press release, Regeneron, MAY 25, 2023, View Source [SID1234632071]). The early clinical trial results, which demonstrated the combination led to clinically meaningful and durable results across multiple clinical settings, will be shared in an oral session at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Monday, June 5 at 3:00 PM CT.

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"LAG-3 inhibitors are known to complement PD-1 inhibitors in the treatment of advanced melanoma. There exists an unmet need to further improve the benefit to patients, including those with liver metastases and other high-risk prognostic markers," said Omid Hamid, M.D., Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, and principal investigator of the trial. "These updated and independent expansion cohort results reinforce the potential of the fianlimab and cemiplimab (Libtayo) combination to deliver clinically meaningful and durable responses in diverse clinical settings and patient populations, with an acceptable safety profile. Particularly encouraging is that the clinical activity was observed in post hoc analyses of patient subgroups, including in patients with a poor prognosis or those who had been previously treated with an anti-PD-1 therapy in the adjuvant setting."

The data to be presented at ASCO (Free ASCO Whitepaper) 2023 include findings from three independent expansion cohorts of adults with unresectable or metastatic melanoma who were all naïve to anti-PD-1 therapy for advanced disease (n=98). Additional follow up will be reported on an initial cohort of first- or second-line patients (n=40) and a confirmatory cohort of first-line patients (n=40), previously reported at ESMO (Free ESMO Whitepaper) 2022. New for this presentation is a cohort of patients who had received prior systemic treatment for melanoma in the neoadjuvant or adjuvant setting (n=18), including adjuvant anti-PD-1 therapy (n=13 of 18).

Tumor responses were based on RECIST 1.1 criteria and per investigator assessment. The median duration of response (DOR) was not reached in any cohort, and the objective response rate (ORR) by cohort was as follows:

Initial cohort: 63% (25 of 40 patients), including 6 complete responses (CR) and 19 partial responses (PR).
Confirmatory cohort: 63% (25 of 40 patients), including 5 CRs and 20 PRs.
Prior neo/adjuvant systemic therapy cohort: 56% (10 of 18 patients). Among the 13 patients in this latest cohort who had prior anti-PD-1 adjuvant treatment, the ORR was 62% (8 of 13 patients), including 1 CR and 7 PRs.
In a post hoc analysis of the three combined cohorts, the ORR was 61% (60 of 98 patients), the median progression-free survival (PFS) was 15 months per Kaplan-Meier estimate (95% CI: 9–NE), and the median follow-up was 13 months (interquartile range 9-19). Additional post hoc analyses found clinically meaningful activity in multiple subgroups of interest, with ORRs in each as follows:

Poor prognosis: 53% (17 of 32 patients) in cases with high baseline lactate dehydrogenase (LDH), 43% (9 of 21 patients) in cases of liver metastasis, and 35% (6 of 17 patients) in cases of M1c stage (visceral metastatic) disease and high baseline LDH.
Varying tumor PD-L1 expression levels: 73% (19 of 26 patients) in cases of ≥1% PD-L1 expression and 56% (23 of 41 patients) in cases of <1% PD-L1 expression.
The safety profile of the fianlimab and Libtayo combination in these expansion cohorts appeared to be generally consistent with the safety profile of Libtayo monotherapy and other anti-PD-(L)1 agents, except for higher rates of adrenal insufficiency, which were ≤Grade 2 in the majority of cases (64%) and all cases were successfully managed with steroid replacement. Adverse events (AEs) occurred in 94% of patients, with 44% being ≥Grade 3 and 30% considered serious. AEs occurring in ≥10% of patients included rash (20%), pruritis (16%), diarrhea (15%), arthralgia (13%), hypothyroidism (12%), adrenal insufficiency (11%) and myalgia (10%). The treatment discontinuation rate due to AEs was 16%.

"Fianlimab in combination with Libtayo has now demonstrated robust response rates in three independent advanced melanoma cohorts – each with unique patient populations," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "These positive results support the clinical potential of fianlimab in combination with Libtayo. We look forward to partnering with the oncology community to further investigate this combination in a broad pivotal clinical development program that includes Phase 3 trials in the advanced and adjuvant melanoma settings, alongside ongoing Phase 2/3 trials in non-small cell lung cancer and research in other solid tumors."

Additional presentations on the fianlimab and Libtayo combination will be shared at ASCO (Free ASCO Whitepaper) during a poster session on Saturday, June 3 from 1:15 to 4:15 PM CT, including:

A Phase 1 study of fianlimab (anti-LAG-3) in combination with cemiplimab (anti-PD-1) in patients with advanced melanoma: poor prognosis subgroup analysis (#9548)
A Phase 3 trial of fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) versus pembrolizumab in patients with previously untreated unresectable locally advanced or metastatic melanoma (#TPS9602)
A Phase 3 trial comparing fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) to pembrolizumab in patients with completely resected high-risk melanoma (#TPS9598)
The potential use of fianlimab and Libtayo described above is investigational, and safety and efficacy of this combination have not been evaluated by any regulatory authority.

On May 25, 2023 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported biomarker data for FLX475 from its ongoing FLX475-02 Phase 1/2 clinical trial which corroborate the clinical activity of FLX475 reported in Epstein-Barr virus-positive (EBV+) lymphoma, EBV+ gastric cancer and non-small cell lung cancer (NSCLC), as well as the mechanism of this novel CCR4 antagonist (Press release, RAPT Therapeutics, MAY 25, 2023, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-present-biomarker-data-corroborating [SID1234632070]). These data will be presented in a poster at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting taking place next week at the McCormick Place Convention Center in Chicago, IL.

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FLX475 is a potent and selective CCR4 antagonist, designed to block the recruitment of immunosuppressive regulatory T cells (Treg) into tumors without affecting healthy tissues. In December 2022 at ESMO (Free ESMO Whitepaper)-IO, a clinical update from the Phase 1/2 trial reported evidence of monotherapy and combination activity. FLX475 monotherapy induced confirmed complete metabolic responses in two of the six evaluable patients with EBV+ NK/T cell lymphoma. In patients with checkpoint inhibitor naïve NSCLC, the overall confirmed objective response rate was 31% (4/13 patients), and the confirmed objective response rate in PD-L1+ tumors was 38% (3/8 patients) following treatment with FLX475 plus pembrolizumab.

As part of the clinical trial protocol, the company analyzed peripheral blood and tumor tissue biomarker data from patients with a broad range of tumor types treated with FLX475 monotherapy. These data substantiate the mechanism of action and support the combination of FLX475 with pembrolizumab. In peripheral blood, FLX475 monotherapy resulted in a small, but significant, increase in the proportion of circulating Treg, consistent with blocking the migration of Treg into the TME. In tumor tissues, changes in the TME conducive to anti-PD(L)1 response were observed. First, FLX475 monotherapy resulted in a decrease in Treg cell populations and an increase in the distance between CD8+ effector T cells and Treg in the TME. Second, transcriptomic profiles from tumors after FLX475 monotherapy exhibited significant changes known to be correlated with an enhanced response to checkpoint inhibitor therapy.

"These biomarker data provide further evidence that FLX475 reduces Treg in the tumor and promotes a permissive environment that should enhance immune-based therapy including checkpoint inhibitors," said Dirk Brockstedt, Ph.D., chief scientific officer of RAPT. "In addition to inhibiting the recruitment of regulatory T cells, which are highly potent suppressors of an antitumor immune response, we saw a concomitant increase in cancer fighting effector T cells and additional beneficial changes in the tumor microenvironment that have been shown to correlate with a favorable response to anti-PD(L)1 therapy. These data are consistent with and support the clinical activity we’ve seen with FLX475 as monotherapy and in combination therapy with pembrolizumab."

About FLX475
FLX475 is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Treg represent a dominant pathway for downregulating the immune response, generally correlate with poor clinical outcomes, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. FLX475 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines, and adoptive T cell therapy.