On September 16, 2024 Ribometrix, a biotechnology company developing small molecule therapeutics that modulate RNA biology, reported the latest data from its eIF4E program at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain, September 13-17 (Press release, Ribometrix, SEP 16, 2024, View Source [SID1234646662]). The poster presentation reviews in vitro and in vivo studies of a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for KRASG12C mutant non-small cell lung cancer (NSCLC). Acquired resistance is observed in most patients treated with the two approved therapies for KRASG12C mutant NSCLC, creating a significant opportunity for a therapy that re-sensitizes tumors to KRAS inhibition. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In less than three years, Ribometrix has advanced its eIF4E program from concept to a lead molecule that has just completed non-GLP toxicology studies," stated Michael Solomon, CEO of Ribometrix, Inc. "The program is a testament to Ribometrix drug discovery capabilities, and the commitment and professionalism of the Ribometrix team. We look forward to moving this program forward into the clinic in collaboration with a partner who shares our vision of its potential to benefit patients, via its novel mechanism of action."

"These data further evidence the broad potential of eIF4E inhibition in multiple tumor types, particularly in combination as a re-sensitizing agent. We have further validated the mechanism of action and characterized the synergistic benefit of RBX-6610, our most advanced eIF4E inhibitor," said Jessica Sorrentino, Ph.D., SVP of Translational Medicine. "RBX-6610 is progressing towards the clinic and we see significant promise for its inclusion with the standard-of-care for both naïve and treatment resistant NSCLC patients, especially whose tumors have KRAS mutations."

Key highlights:

RBX-6610 demonstrated consistent anti-proliferative effects in KRASG12C mutant tumor cell lines, in both treatment-naïve lines and those with acquired resistance.
Additionally, the combined in vitro effects of co-treatment of RBX-6610 with KRAS inhibitors were synergistic, such that the proliferative inhibitory effects were greater than the sum of either treatment alone. Mechanistically, this was due to an induction of apoptosis, specific to co-treatment in treatment-naïve tumor cells as well as cells resistant to KRAS inhibitors. This synergistic phenotype was observed with both approved KRAS inhibitors, as well as investigational RAS inhibitors.
Daily oral RBX-6610 monotherapy led to substantial tumor growth inhibition in both treatment naïve and resistant KRASG12C NSCLC xenograft model (75% vs 71% TGI, respectively), corroborating the anti-proliferative effects seen in vitro.
In combination with sotorasib, an approved KRAS inhibitor, daily oral treatment with RBX-6610 led to significant tumor regression and improved survival in both the treatment-naïve and sotorasib resistant setting (34% and 49% mean tumor regression respectively). No toxicity was observed in up to 35 days of daily oral treatment across all cohorts.
In vitro data demonstrated improved selectivity of cap dependent translation inhibition by RBX-6610 relative to other translation inhibitors including zotatifin, an eIF4A inhibitor.
Ribometrix continues to generate data demonstrating the multi-tumor therapeutic potential of eIF4E inhibition. Studies in melanoma and breast cancer were presented at the Society for Melanoma Research and the San Antonio Breast Cancer Symposium in 2023, and data across melanoma, colorectal, breast, and non-small cell lung cancer were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in 2024. Data have repeatedly included support for both monotherapy and combination regimens as well as the potential to re-sensitize to standard-of-care treatments.

The ESMO (Free ESMO Whitepaper) poster is now available to view on the "Publications" page of Ribometrix’s website.

About eIF4E

Eukaryotic translation initiation factor 4E (eIF4E) is a crucial regulatory component of mRNA translation and well-documented driver of oncogenesis. Clinically, eIF4E activity is elevated in many tumor indications and it is typically associated with poor prognosis. Targeting eIF4E has the potential to enhance anti-cancer activity when given in combination with standard-of-care. Additionally, eIF4E inhibition has the potential to overcome drug resistance and re-sensitize tumors to anti-cancer therapies. Based on substantial external and in-house data, Ribometrix is developing eIF4E inhibitors as a promising combination therapy approach and treatment for treatment-resistant tumors.

On September 16, 2024 PDS Biotechnology Corporation (Nasdaq: PDSB) ("PDS Biotech" or the "Company"), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines, reported updated data from the VERSATILE-002 trial evaluating Versamune HPV (formerly PDS0101) in combination with KEYTRUDA (pembrolizumab) as a first-line (1L) treatment for patients with HPV16-positive recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (Press release, PDS Biotechnology, SEP 16, 2024, View Source [SID1234646661]). The data were presented during a poster session on September 14 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of the latest data cut of the VERSATILE-002 single-arm, Phase 2 trial on May 17, 2024, Versamune HPV plus pembrolizumab continued to be well tolerated in this 1L R/M HPV16-positive HNSCC population. Enrollment in the trial (n=53) is complete, 10 patients remain on study treatment and 27 patients (including the 10 on treatment) continue to be followed for survival. Median patient follow-up is 16 months. The data demonstrated the following:

•
Median Overall Survival (mOS) was 30 months with a lower 95% confidence interval of 19.7 months; Published mOS for pembrolizumab is 12-18 months1,2

•
Objective Response Rate (ORR) of 36% (19/53); Published ORR for pembrolizumab is 19-25%1,2

•
Disease Control Rate (DCR) is 77% (41/53)

•
21% (11/53) of patients had deep tumor responses and shrinkage of 90-100%

•
9% (5/53) of patients had a complete response

•
Treatment-related adverse events of Grade ≥3 were seen in 9 patients (Grade 3, n=8 and Grade 4, n=1)

"The updated response data we presented at ESMO (Free ESMO Whitepaper) show the strong clinical activity and durability of Versamune HPV plus pembrolizumab," said Jared Weiss, M.D., Section Chief of Thoracic and Head/Neck Oncology, Professor of Medicine at the University of North Carolina, and principal investigator of the VERSATILE-002 clinical trial. "Continued evaluation shows the promise of this combination in improving survival for patients with HPV16-positive HNSCC."

A global, randomized, controlled Phase 3 clinical trial, VERSATILE-003, that will evaluate Versamune HPV plus pembrolizumab vs. pembrolizumab monotherapy as 1L treatment in patients with HPV16-positive R/M HNSCC with CPS ≥1 is planned to start this year.

"We’re encouraged to see that as the data from our VERSATILE-002 clinical trial have matured, responses continue to improve, suggesting durability of the Versamune HPV induced anti-tumor immune response," said Dr. Kirk Shepard, M.D., Chief Medical Officer of PDS Biotech. "The encouraging patient survival and clinical responses coupled with promising tolerability as seen in the VERSATILE-002 trial underscore our belief in the potential of the combination to be the first HPV-targeted immunotherapy for HNSCC, and a significant advancement in the treatment of the growing population of patients with HPV16-positive HNSCC. We are working toward initiating the VERSATILE-003 Phase 3 study this year."

Versamune HPV has been granted Fast Track designation by the FDA.

1.
Harrington K. et al. J Clin Oncol. 2022 ascopubs.org/journal/jco on October 11, 2022: DOI View Source

2.
Licitra L. et al. 2024, International Journal of Radiation Oncology Volume 118, Issue 5e2-e3April 01
No head-to-head studies have been performed comparing Versamune HPV with other treatments

On September 14, 2024 NuCana plc (NASDAQ: NCNA) reported final data from the Phase 2 NuTide:701 study at the ESMO (Free ESMO Whitepaper) Congress on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor therapy (Press release, Nucana, SEP 16, 2024, View Source [SID1234646660]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In this cohort of 12 patients, most of whom had received at least two prior lines of PD-1 inhibitor therapy, nine (75%) achieved disease control, including two patients who achieved Partial Responses. One of these patients, who had received two prior lines of PD-1 inhibitor-based therapy and had progressed on their latest treatment of ipilimumab plus nivolumab within two months, achieved a 55% reduction in tumor volume. Seven of the 12 patients had a progression free survival time of greater than five months, which is highly atypical in this patient population. In addition to achieving these encouraging efficacy signals, the combination of NUC-7738 and pembrolizumab had a favorable safety profile.

NUC-7738’s ability to sensitize PD-1 resistant tumors to rechallenge with PD-1 inhibitors is believed to be due to its ability to target multiple aspects of the tumor microenvironment (TME) via the disruption of RNA polyadenylation and subsequent changes to gene expression in cancer cells. In support of this hypothesis, data presented from tumor biopsies obtained before and after NUC-7738 based treatment demonstrated increases in genes related to antigen presentation and T-cell activation.

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We are very excited to share these data on NUC-7738 in combination with pembrolizumab in PD-1 inhibitor refractory and resistant patients with melanoma. Outcomes in this patient population are very poor, with median progression free survival of 2-3 months with the current standard of care, so we are very encouraged that the majority of patients who received this combination achieved a progression free survival of more than five months."

Mr. Griffith continued: "The translational data that has been generated in this study and in previous non-clinical studies give us confidence that the effects we are seeing are a result of NUC-7738 making previously resistant tumors sensitive to rechallenge with PD-1 inhibitors by targeting multiple aspects of the tumor microenvironment. Our data on NUC-7738 obtained in other tumor types indicate that this phenomenon is not restricted to melanoma and that NUC-7738 may have the ability to sensitize other PD-1 inhibitor resistant tumor types. We look forward to sharing our development plans for NUC-7738 in the near future."

On September 17, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that targets B7-H3, for patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, MacroGenics, SEP 16, 2024, View Source [SID1234646659]). The data were featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain from September 13-17, 2024.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"A key reason for conducting the TAMARACK study was to test the hypothesis that we could improve upon the duration of vobra duo treatment observed in the Phase 1 study by reducing the starting dose from 3.0 mg/kg to either 2.0 or 2.7 mg/kg and increasing the dosing interval from every three weeks to every four weeks. In doing so, our aim was to improve safety and tolerability, extend the treatment duration and achieve improved rPFS as compared to the result in our Phase 1 mCRPC dose expansion cohort," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We believe that these latest results from TAMARACK continue to demonstrate that vobra duo is an active drug in prostate cancer. Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025. We expect to make decisions about potential future development in the context of a competitive treatment landscape assessment, resource allocation across our clinical portfolio and potential partnering opportunities for vobra duo."

TAMARACK Study Demographics

The abstract submitted to ESMO (Free ESMO Whitepaper) was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024, are included below and are reported in the Company’s poster presentation at ESMO (Free ESMO Whitepaper).
The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival.
Baseline Characteristics:
•Enrolled study participants had a median age of 70 years (range, 35-89).
•88 Study participants (48.6%) had an ECOG performance status of 1 or 2.
•30 Study participants (16.6%) had visceral disease at baseline, with liver or lung disease in 25 participants (13.8%).
•81 Study participants (44.8%) had measurable disease at baseline, and 97 (53.6%) had received prior taxane.
•Both treatment arms were well-balanced across most baseline characteristics, including prior use of taxanes, androgen receptor axis-targeted (ARAT) treatment, poly-ADP ribose polymerase (PARP) treatment, and baseline PSA.
TAMARACK Efficacy Results as of July 9, 2024 Cut-off Date
Overall, the Company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival (rPFS) rate, as well as other measures of tumor response.
•In the intent-to-treat (ITT) population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg arm (95% CI, 58-79).
•Landmark 6-month rPFS rates were consistent across taxane-naïve study participants (ranging from 66-82%) and taxane pre-treated study participants (ranging from 60-73%), regardless of treatment arm.

•Although immature, with only 65 PFS events (35.9%) as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7 mg/kg cohort (95% CI, 7.2-10.6). Because these results were immature as of the cutoff date, they are likely to change as additional events accrue.
Tumor response rates
•Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9) and the unconfirmed ORR was 26.7% (n=12).
•Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was 46.9% (n=15).
•Confirmed ORR was comparable between taxane-naïve study participants (26.7%, n=12/45) and taxane pre-treated study participants (17.5%, n=11/63), regardless of treatment arm.
•Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age.
TAMARACK Safety Results as of July 9, 2024 Cut-off Date
Overall summary of adverse events (AEs)
•In the 2.0 mg/kg cohort, 65.6% of study participants (n=59) experienced a Grade ≥3 treatment-emergent AE (TEAE); this cohort had a discontinuation rate of 25.6% (n=23) and a dose reduction rate of 50.0% (n=45) due to TEAEs.
•In the 2.7 mg/kg cohort, 62.8% of study participants (n=54) experienced a Grade ≥3 TEAE; this cohort had a discontinuation rate of 38.4% (n=33) and a dose reduction rate of 54.7% (n=47) due to TEAEs.
•The most common (occurring in ≥20% of study participants) all-grade TEAEs were: asthenia, edema peripheral, decreased appetite, nausea, pleural effusion, diarrhea, fatigue, constipation, anemia, palmar-plantar erythrodysesthesia (PPE, or hand-foot syndrome), neutropenia, and stomatitis. The majority of TEAEs with a ≥10% incidence rate in either treatment arm was limited to Grade 1/2 events.
•Rates of pleural effusion, pericardial effusion, and PPE for both the 2.0 mg/kg cohort (28.8%, 13.3%, 18.9%, respectively) and the 2.7 mg/kg cohort (44.2%, 17.5%, 28%, respectively) decreased compared to the Phase 1 mCRPC dose expansion cohort (48.8%, 17.1%, 46.3%, respectively), despite an increased median number of doses of vobra duo administered on TAMARACK.

•Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage.
•Rates of treatment-related AEs (including all grades and Grade ≥3) and treatment-related severe AEs were similar between taxane-naïve and taxane pre-treated study participants.

Tolerability findings

•In the 2.0 mg/kg cohort, 25.6% of study participants (n=23) remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses (range, 1-11), with a median dose intensity (calculated as a percentage of the total planned dose that was administered) of 92.6% (range, 64.2-106.1%).
•In the 2.7 mg/kg cohort, 18.6% of study participants (n=16) remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses (range, 1-12), with a median dose intensity of 81.7% (range, 40.5-104.3%).
•Taxane-naïve study participants experienced higher rates of dose reductions due to TEAEs (62.7%) and dose interruptions due to TEAEs (70.7%) compared to taxane pre-treated study participants (44.6% and 43.6%, respectively).

ESMO Poster Presentation

Title: TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST
The poster presentation is available for download under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source

Conference Call

The Company will host a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00am ET. The call will be led by Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President – Chief Medical Officer; and Jim Karrels, Senior Vice President – Chief Financial Officer.

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

About Vobra Duo and the TAMARACK Study

Vobra duo is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation. The TAMARACK Phase 2 study of vobra duo is being conducted in participants with mCRPC who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

On September 16, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS) ("iTeos"), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported follow-up interim data from GALAXIES Lung-201, the Phase 2 platform study sponsored by iTeos’ development partner GSK, assessing the belrestotug + dostarlimab doublet in previously untreated, unresectable, locally advanced or metastatic PD-L1 high non-small cell lung cancer (NSCLC) (Press release, iTeos Therapeutics, SEP 16, 2024, View Source [SID1234646658]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are encouraged by this interim cut of GALAXIES Lung-201 data in which a clinically meaningful, investigator-assessed Objective Response Rate was observed with belrestotug in combination with dostarlimab in first-line, PD-L1 high non-small cell lung cancer patients. Further, with roughly 60 percent confirmed ORR at three distinct doses and a meaningful difference of 30 percent compared to dostarlimab alone, we believe this underscores the potential differentiation of our TIGIT:PD-1 doublet," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "The improvement in depth of response in tumor measurement in patients treated with the doublet compared to those treated with PD-1 alone holds promising therapeutic potential for a patient population with limited options. We believe these encouraging data further support the recent initiation of GALAXIES Lung-301, the registrational Phase 3 trial assessing the TIGIT:PD-1 doublet in the same indication and setting. Based on these results, we are committed to leveraging our science to impact the lives of people living with cancer and are excited to see longer-term follow-up data in 2025."

"While checkpoint inhibitor therapies have played a significant role in how we treat non-small cell lung cancer, the medical community continues to look for new patient-centered treatment options to meaningfully improve this life-threatening condition," said Brian Henick, M.D., interim director of experimental therapeutics and director of translational research in upper-aerodigestive malignancies in medical oncology of Columbia University Irving Medical Center. "The follow-up interim analysis from the GALAXIES Lung-201 study represent promising progress and the deep responses observed in the belrestotug + dostarlimab doublet provide a strong, consistent signal.

We eagerly anticipate gaining further insights from this trial over the next year as the dataset matures."

Highlights of Interim GALAXIES Lung-201 Data

As of the June 7, 2024 data cutoff, the late-breaking interim data presented at the ESMO (Free ESMO Whitepaper) Congress were based on 124 patients eligible for safety and efficacy evaluation (modified intention-to-treat ≥5.6 months follow-up). Patients received dostarlimab or belrestotug + dostarlimab at the following dose levels: dostarlimab 500mg, belrestotug 100mg + dostarlimab 500mg (Dose A), belrestotug 400mg + dostarlimab 500mg (Dose B), and belrestotug 1000mg + dostarlimab 500mg (Dose C).

•
Clinically meaningful improvement in the primary endpoint of ORR was observed consistently across each belrestotug + dostarlimab cohort (63.3% Dose A, 65.6% Dose B and 76.7% Dose C compared to 37.5% with dostarlimab alone). cORR, defined as complete or partial response confirmed by repeat imaging ≥4 weeks after response criteria first met, was roughly 60.0% for each dose compared to 28.1% cORR for dostarlimab alone.
•
Of the patients with evaluable paired ctDNA samples (baseline and week 7), median ctDNA reduction was 65% for dostarlimab monotherapy compared to 55% for Dose A, 94% for Dose B, and 97% for Dose C.
•
Belrestotug + dostarlimab led to an increase in immune-related adverse events compared to dostarlimab monotherapy, which were generally manageable. The safety profile of belrestotug in combination with dostarlimab has been broadly consistent with the known safety profile of combination therapy with checkpoint inhibitors. The most frequent treatment-related adverse events (≥15%) were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%), both commonly observed with immunotherapies.

Response measure in mITT

Dostarlimab

(N=32)

Dose A: Dostarlimab +
belrestotug

100 mg

(N=30)

Dose B: Dostarlimab +
belrestotug

400 mg

(N=32)

Dose C: Dostarimab +
belrestotug

1000 mg

(N=30)

Median follow-up, months (range)

7.0 (0.2–16.6)

8.5 (0.3–14.3)

8.5 (0.4–16.2)

6.7 (2.4–9.7)

ORR,1,2%
n (95% CI)

37.5% n=12 (21.1–56.3)

63.3%
n=19 (43.9–80.1)

65.6%
n=21 (46.8–81.4)

76.7%
n=23 (57.7–90.1)

Complete response, n (%)

0

0

0

0

Partial response, n (%)

12 (37.5%)

19 (63.3%)

21 (65.6%)

23 (76.7%)

Stable disease, n (%)

14 (43.8%)

5 (16.7%)

4 (12.5%)

5 (16.7%)

Progressive disease, n (%)

2 (6.3%)

4 (13.3%)

3 (9.4%)

2 (6.7%)

Not evaluable/no assessment,3 n (%)

4 (12.5%)

2 (6.7%)

4 (12.5%)

0

Confirmed ORR,2 %
n (95% CI)

28.1%
n=9 (13.7–46.7)

60.0%
n=18 (40.6–77.3)

59.4%
n=19 (40.6–76.3)

63.3%
n=19 (43.9–80.1)

1. unconfirmed ORR; 2. PD-L1 high (TPS ≥50%) was determined locally or centrally by DAKO 22C3 or VENTANA SP263 assay; 3. patients who only had "not evaluable" post baseline assessments, those who had a best response of "not evaluable" per RECIST 1.1 criteria, or those where no post-baseline tumor assessment was performed; CI, confidence interval

Conference Call Details

The follow-up interim data from GALAXIES Lung-201 will be discussed during a conference call and webcast presentation on Monday, September 16th, 2024 at 8:00AM ET. To register for the webcast presentation, please visit the Events section on the Investors page of the iTeos website at investors.iteostherapeutics.com. A webcast replay may be accessed on the Investors section of the iTeos website.

Phase 2 GALAXIES Lung-201 Trial Design

The Phase 2 GALAXIES Lung-201 study is a randomized, open-label, global platform study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with PD-L1 high (TPS ≥50%), previously untreated, unresectable, locally advanced or metastatic NSCLC.​ Arms and interventions in this study include: pembrolizumab (anti-PD-1) monotherapy, dostarlimab (anti-PD-1) monotherapy, belrestotug (anti-TIGIT) + dostarlimab doublet combination, and belrestotug + dostarlimab + nelistotug (anti-CD96) triplet combination.

The primary endpoint of the study is investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include safety and additional efficacy measures such as progression free survival, overall survival, and duration of response.