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.

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"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]).

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"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.

On September 16, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) reported final data from the CABINET Phase III trial investigating Cabometyx (cabozantinib) versus placebo in people living with advanced pancreatic neuroendocrine tumors (pNETs) or advanced extra-pancreatic neuroendocrine tumors (epNETs) whose disease had progressed after prior systemic therapy (Press release, Ipsen, SEP 16, 2024, View Source [SID1234646657]). These data demonstrated a statistically significant reduction in the risk of disease progression or death for Cabometyx versus placebo of 77% (hazard ratio (HR) 0.23) and 62% (HR 0.38) for people living with advanced pNETs and epNETs, respectively.1,2 Presentation of these data is taking place today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: NETs and Endocrine Tumors at 2:45 p.m. CEST, and is published in the New England Journal of Medicine (NEJM).

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"People living with neuroendocrine tumors face many challenges, from securing a timely diagnosis to optimal treatment options which address the needs of the increasing number of people affected by this cancer worldwide," said Teodora Kolarova, Executive Director, International Neuroendocrine Cancer Alliance. "These latest data reaffirm the possibilities of continuing scientific advancements in neuroendocrine tumors, offering the potential for new therapies which could significantly impact people’s everyday lives as they navigate this complex and life altering diagnosis."

Final results demonstrated progression-free survival (PFS) benefits in favor of Cabometyx versus placebo by blinded independent central review (BICR).1,2 In the pNET cohort, at a median follow-up of 13.8 months, median PFS was 13.8 months for Cabometyx versus 4.4 months for placebo (HR 0.23 [95% confidence interval (CI) 0.12-0.42] p<0.0001).1,2 In the epNET cohort, at a median follow-up of 10.2 months, median PFS was 8.4 months for Cabometyx versus 3.9 months for placebo (HR 0.38 [95% CI 0.25-0.59] p<0.0001).1,2 The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were identified.1,2

"These latest data reinforce the potential of Cabometyx to deliver significant efficacy benefits at an advanced stage of disease," said Christelle Huguet, EVP and Head of Research and Development at Ipsen. "Through our submission to the EMA, it is our ambition to evolve the treatment paradigm for people living with neuroendocrine tumors, harnessing our longstanding heritage in this area to deliver an effective new therapy where options are notably limited."

The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.5,6 However, despite increasing awareness, the non-specific nature of NET symptoms often leads patients to be seen by multiple specialists and to undergo various forms of testing before an accurate diagnosis is achieved.5 As a result, almost a third of people take at least five years to be diagnosed with NETs, contributing to poorer patient outcomes.5 Most forms of NETs are indolent in nature and can develop in any part of the body,7 requiring multiple lines of therapy as people progress.3,4 Treatment options upon progression are often limited dependent on primary site of disease, resulting in challenges in identifying optimal care pathways specific to patients’ circumstances.

On September 16, 2024 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX:1541, "ImmuneOnco") reported the global registrational strategy for the PD-L1xVEGF bispecific antibody SYN-2510/IMM2510 in combination with chemotherapy in front-line non-small cell lung cancer (NSCLC) and in front-line triple-negative breast cancer (TNBC) (Press release, Instil Bio, SEP 16, 2024, View Source [SID1234646655]).

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In China, ImmuneOnco is accelerating the development of IMM2510/SYN-2510 in front-line NSCLC by targeting initiation in late 2024 of a Phase 1b/2 front-line chemo combination study. This study is expected to enroll patients with driver gene mutation-negative non-squamous and squamous NSCLC. ImmuneOnco is also accelerating development of IMM2510/SYN-2510 in front-line TNBC with initial Phase 1b/2 chemotherapy combination studies targeted to begin in early 2025.

In the United States, Instil is prioritizing development of SYN-2510/IMM2510 in NSCLC and TNBC. US IND submission is targeted for late 2024, starting with a Phase 2 trial of SYN-2510/IMM2510 monotherapy in second-line non-squamous and squamous NSCLC.

With potential positive proof-of-concept data, ImmuneOnco and Instil may initiate joint global randomized Phase 3 chemotherapy combination trials in first-line non-squamous and squamous NSCLC and/or first-line TNBC.

"There are significant unmet medical needs in NSCLC and TNBC cancer patients which may be addressed by IMM2510," said Dr. Wenzhi Tian, PhD, CEO and CSO of ImmuneOnco. "This practical and accelerated registrational strategy, which is aligned with Instil, paves a clear pathway to a potential regulatory approval for us in China and for Instil Bio globally."

"SYN-2510 may have the opportunity to meaningfully improve on the current standard of care in NSCLC and TNBC," said Bronson Crouch, CEO of Instil. "Our expectation for the initial US study of SYN-2510 is that it would lay a foundation for the efficient enrollment of potential global Phase 3 studies."

About SYN-2510/IMM2510

SYN-2510/IMM2510 is a PD-L1xVEGF bispecific antibody in development for the treatment of multiple solid tumor cancers. SYN-2510/IMM2510 is differentiated from other PD-(L)1xVEGF bispecific antibodies by its VEGF trap, which binds multiple VEGF receptor ligands beyond VEGF-A, a bispecific structure which leverages PD-L1 as an anchor in the tumor microenvironment (TME), and enhanced antibody-dependent cellular cytotoxicity (ADCC) to direct killing of PD-L1-positive tumor cells.

On September 16, 2024 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 Phase 1 data with brenetafusp in patients with platinum resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Immunocore, SEP 16, 2024, View Source [SID1234646654]). In a proffered session to be held on Monday, September 16, 2024, the Company will present translational Phase 1/2 data with KIMMTRAK (tebentafusp-tebn) and brenetafusp demonstrating that T cell fitness gene expression signature in blood is an important parameter associated with clinical activity for both therapies in metastatic uveal melanoma.

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"Brenetafusp monotherapy is active in heavily pre-treated, platinum resistant ovarian cancer patients and can be combined safely with chemotherapy. We see the hallmarks of ImmTAC clinical activity in this Phase 1 data, such as disease control, ctDNA molecular response, and association with T cell fitness, which increases our confidence in the potential for brenetafusp in ovarian cancer," said David Berman, Head of Research and Development. "While early, the promising efficacy data from chemotherapy plus brenetafusp led us to expand the combinations we are studying, including in earlier-line platinum sensitive disease."

Dr. Claire Friedman, Gynecologic Medical Oncologist & Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center, said: "While many solid tumors have benefited from the advances in immunotherapy, the treatment of recurrent ovarian cancer has remained an ongoing challenge. These data offer proof of concept that patients with advanced, platinum-resistant ovarian cancer can benefit from brenetafusp, alone or in combination with chemotherapy, and support further development of the drug in this patient population."

Phase 1 monotherapy data in heavily pre-treated platinum resistant ovarian cancer patients

Thirty-seven patients with heavily pre-treated (median 5 prior lines) serous ovarian cancer were treated with brenetafusp monotherapy, including four patients previously presented in the efficacy data set at ESMO (Free ESMO Whitepaper) 2022. A majority of patients had received prior bevacizumab (81%) and PARP inhibitors (59%).

Brenetafusp was well tolerated with no treatment-related discontinuation or death observed. The most frequent treatment-related adverse event was reversible and manageable cytokine release syndrome, observed in 57% of patients, with the majority being Grade 1.

Thirty-one of the 37 monotherapy patients were evaluable for RECIST v1.1 tumor assessment, 58% of whom demonstrated disease control (partial response and stable disease), including two confirmed partial responses (6.5% RECIST response rate). Of patients who had tumor progression, 64% were treated beyond progression (median of 2 additional months). Across all 37 patients, the median progression-free survival (PFS) was 3.3 months, and the overall survival (OS), while still maturing, was 73% at 6 months.

Of the 29 monotherapy patients evaluable for circulating tumor DNA (ctDNA) response, 31% (9/29) had a molecular response (≥0.5 log reduction by week 9).

Twenty-eight monotherapy patients were evaluable for baseline blood T cell fitness (TCF) gene expression signature. There was greater activity in patients with a TCF signature above median versus those at or below the median, respectively, including: disease control (80% vs 38%), PFS (3.7 months vs 2.2 months) and six-month OS (93% vs 47%).

Phase 1 chemotherapy combination data in heavily pre-treated platinum resistant ovarian cancer patients

As presented today at ESMO (Free ESMO Whitepaper) in a pre-clinical study poster (1021P), the combination of chemotherapy with brenetafusp has the potential to enhance clinical activity by increasing expression of the antigen presentation machinery in cancer cells.

In the Phase 1 trial, 16 patients with platinum-resistant ovarian cancer were treated with brenetafusp and either gemcitabine, nab-paclitaxel or pegylated doxorubicin chemotherapy. These patients were heavily pre-treated (median of 4 prior treatment lines) including prior bevacizumab (75%) and PARP inhibitors (75%). The safety profile of brenetafusp in combination with chemotherapy was consistent with the expected profile of each individual agent.

Thirteen of the 16 combination patients were evaluable for RECIST v1.1 tumor assessment. All 13 patients received prior platinum and taxane therapy, and 6 received prior gemcitabine. Sixty nine percent (9/13) of patients achieved disease control, including three partial responses (23% RECIST response rate). Historical chemotherapy efficacy data in this heavily pre-treated patient population is sparse but indicate response rates are less than 10%, with disease control rates typically ~40-50%1.

Eleven of the 16 combination patients were evaluable for ctDNA response. The molecular response rate was 82% (9/11). As previously reported for brenetafusp in cutaneous melanoma (ASCO 2024), ctDNA molecular response in this trial was also associated with longer OS and PFS.

T cell fitness associated with clinical benefit across ImmTAC platform and in different tumor types

At an oral proffered session on Monday, September 16, 2024, the Company will present translational data from previously treated, metastatic uveal melanoma (mUM) patients, including 132 patients treated with KIMMTRAK in a Phase 1/2 trial, and 22 patients treated with brenetafusp in a Phase 1 trial.

In the KIMMTRAK cohort, patients with a TCF signature greater than or equal to the median had higher clinical activity compared to patients with a TCF signature below the median, respectively, including longer OS (28 months vs 11 months), PFS (5 months vs 2 months) and disease control (67% vs 36%). The association of TCF signature with longer OS was independent of known prognostic factors in uveal melanoma. In addition, the TCF signature was associated with greater tumor reduction and a higher rate of on-target, melanocyte-related adverse events; both are consistent with the mechanism of action, and suggest that the signature is not purely prognostic.

This TCF signature, discovered for KIMMTRAK in mUM, was subsequently confirmed as an important parameter of clinical activity for brenetafusp in mUM (ESMO 2024), ovarian cancer (ESMO 2024), and cutaneous melanoma (ASCO 2024). The accumulating data suggests that ImmTAC therapies may deliver greater clinical activity in earlier line patients, where TCF is expected to be higher, leading the Company to investigate brenetafusp in these populations.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in ovarian, NSCLC, and endometrial cancers. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp.

About Ovarian Cancer

Most patients with ovarian cancer are diagnosed with advanced disease, giving it the highest mortality amongst gynecological malignancies in the US and Europe. The current standard of care is surgery followed by platinum-based chemotherapy, and although many patients initially respond, the disease often recurs and, over time, becomes resistant to further platinum therapy. There is significant unmet need for new therapies that improve clinical outcomes in both platinum-sensitive and platinum-resistant ovarian cancer patients.

About Uveal Melanoma

Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

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.

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).

About KIMMTRAKConnect

Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.