Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer
Immunocore Holdings plc (Nasdaq: IMCR) presented Phase 1 data for brenetafusp, an ImmTAC bispecific targeting PRAME, in platinum-resistant ovarian cancer patients at the 2024 ESMO Congress. Key findings include:
1. Monotherapy: 58% disease control rate, 6.5% RECIST response rate, and 3.3 months median PFS in heavily pre-treated patients.
2. Chemotherapy combination: 69% disease control rate and 23% RECIST response rate.
3. T cell fitness (TCF) gene expression signature in blood associated with improved clinical outcomes across different tumor types.
The data suggests potential for brenetafusp in ovarian cancer, particularly in earlier-line treatment where TCF is expected to be higher.
Immunocore Holdings plc (Nasdaq: IMCR) ha presentato i dati di Fase 1 per brenetafusp, un ImmTAC bispecifico che mira a PRAME, in pazienti con cancro ovarico resistente al platino durante il Congresso ESMO 2024. Le principali scoperte includono:
1. Monoterapia: tasso di controllo della malattia del 58%, tasso di risposta RECIST del 6,5% e una sopravvivenza libera da progressione mediana di 3,3 mesi in pazienti con precedenti trattamenti intensivi.
2. Combinazione con chemioterapia: tasso di controllo della malattia del 69% e tasso di risposta RECIST del 23%.
3. Firma di espressione genica di fitness delle cellule T (TCF) nel sangue associata a risultati clinici migliorati attraverso diversi tipi di tumore.
I dati suggeriscono il potenziale di brenetafusp nel cancro ovarico, in particolare nel trattamento nelle fasi iniziali dove si prevede che il TCF sia più elevato.
Immunocore Holdings plc (Nasdaq: IMCR) presentó datos de Fase 1 para brenetafusp, un ImmTAC biespecífico que se dirige a PRAME, en pacientes con cáncer de ovario resistente al platino en el Congreso ESMO 2024. Los hallazgos clave incluyen:
1. Monoterapia: tasa de control de la enfermedad del 58%, tasa de respuesta RECIST del 6.5% y una mediana de PFS de 3.3 meses en pacientes con múltiples tratamientos previos.
2. Combinación con quimioterapia: tasa de control de la enfermedad del 69% y tasa de respuesta RECIST del 23%.
3. Firma de expresión génica de aptitud de células T (TCF) en sangre asociada con resultados clínicos mejorados en diferentes tipos de tumores.
Los datos sugieren el potencial de brenetafusp en el cáncer de ovario, especialmente en el tratamiento en líneas más tempranas donde se espera que el TCF sea más alto.
Immunocore Holdings plc (Nasdaq: IMCR)는 2024 ESMO 컨gress에서 brenetafusp에 대한 1상 데이터를 발표했습니다. 이는 PRAME을 표적으로 하는 이중특이적 ImmTAC으로, 백금 저항성 난소암 환자에서 사용됩니다. 주요 결과는 다음과 같습니다:
1. 단독요법: 질병 조절률 58%, RECIST 반응률 6.5%, 중증도 치료를 많이 받은 환자에서 중앙 무진행 생존기간(PFS) 3.3개월입니다.
2. 화학요법 병용: 질병 조절률 69%, RECIST 반응률 23%입니다.
3. T 세포 적합성 (TCF) 유전자 발현 서명이 다양한 종양 유형에서 임상 결과 개선과 관련이 있습니다.
이 데이터는 난소암에서 brenetafusp의 잠재력을 제시하며, 특히 TCF가 더 높을 것으로 예상되는 초기 치료에서 유망합니다.
Immunocore Holdings plc (Nasdaq: IMCR) a présenté des données de phase 1 pour brenetafusp, un ImmTAC bispécifique ciblant PRAME, chez des patients atteints de cancer de l'ovaire résistant au platine lors du Congrès ESMO 2024. Les résultats clés incluent:
1. Monothérapie: taux de contrôle de la maladie de 58%, taux de réponse RECIST de 6,5% et une médiane de PFS de 3,3 mois chez des patients ayant reçu de nombreux traitements antérieurs.
2. Association avec la chimiothérapie: taux de contrôle de la maladie de 69% et taux de réponse RECIST de 23%.
3. Signature d'expression génique de fitness des cellules T (TCF) dans le sang associée à des résultats cliniques améliorés dans différents types de tumeurs.
Les données suggèrent un potentiel pour brenetafusp dans le cancer de l'ovaire, en particulier dans les traitements en première ligne où le TCF est censé être plus élevé.
Immunocore Holdings plc (Nasdaq: IMCR) stellte auf dem ESMO-Kongress 2024 Daten der Phase 1 für brenetafusp vor, ein ImmTAC-Bispezifikum, das PRAME bei Patienten mit platinresistentem Eierstockkrebs anvisiert. Die wichtigsten Erkenntnisse umfassen:
1. Monotherapie: 58% Ansprechrate bei der Krankheitskontrolle, 6,5% RECIST-Ansprechrate und eine mediane PFS von 3,3 Monaten bei stark vorbehandelten Patienten.
2. Kombination mit Chemotherapie: 69% Ansprechrate bei der Krankheitskontrolle und 23% RECIST-Ansprechrate.
3. T-Zell Fitness (TCF) Genexpressionssignatur im Blut assoziiert mit verbesserten klinischen Ergebnissen bei verschiedenen Tumortypen.
Die Daten deuten auf das Potenzial von brenetafusp bei Eierstockkrebs hin, insbesondere bei früheren Behandlungen, bei denen TCF voraussichtlich höher sein wird.
- Brenetafusp monotherapy showed 58% disease control rate in heavily pre-treated platinum-resistant ovarian cancer patients
- Brenetafusp + chemotherapy combination achieved 69% disease control rate and 23% RECIST response rate
- T cell fitness gene expression signature associated with improved clinical outcomes across tumor types
- No treatment-related discontinuations or deaths observed in monotherapy group
- 82% molecular response rate in ctDNA for combination therapy patients
- Only 6.5% RECIST response rate for brenetafusp monotherapy
- Median progression-free survival of 3.3 months for monotherapy patients
- 57% of monotherapy patients experienced cytokine release syndrome, though mostly Grade 1
Insights
The Phase 1 data for brenetafusp in platinum-resistant ovarian cancer shows promising results. 58% of evaluable patients demonstrated disease control, including a 6.5% RECIST response rate. The median PFS of 3.3 months and 73% 6-month OS are encouraging for this heavily pre-treated population. The 31% ctDNA molecular response rate further supports the drug's activity. Importantly, patients with higher T cell fitness (TCF) signatures showed better outcomes, suggesting a potential biomarker for patient selection. The combination with chemotherapy yielded even more impressive results, with a 69% disease control rate and 23% RECIST response rate. These outcomes surpass historical chemotherapy efficacy data in similar populations. The association of TCF with clinical benefit across different tumor types indicates a broader potential for ImmTAC therapies.
The data presented for brenetafusp is particularly intriguing for ovarian cancer treatment. Platinum-resistant ovarian cancer has been a challenging area with effective options. The safety profile of brenetafusp, with no treatment-related discontinuations or deaths, is noteworthy. The manageable cytokine release syndrome in 57% of patients, mostly Grade 1, is acceptable for this patient population. The ability to combine brenetafusp with various chemotherapies without significant additional toxicity is promising for future treatment strategies. The molecular response rate of 82% in the combination cohort is impressive and could potentially translate to improved long-term outcomes. The correlation between T cell fitness and clinical benefit suggests a potential for personalized treatment approaches, which could be a game-changer in ovarian cancer management.
Immunocore's brenetafusp data presents a significant market opportunity. The ovarian cancer therapeutics market is projected to grow substantially and effective treatments for platinum-resistant cases are in high demand. The positive efficacy signals, especially in combination with chemotherapy, position brenetafusp as a potential future standard of care. The T cell fitness biomarker could lead to a companion diagnostic, enhancing the drug's market positioning and potentially improving reimbursement prospects. The safety profile supports the possibility of moving to earlier treatment lines, which could expand the addressable patient population. The consistency of the T cell fitness signature across tumor types suggests broader applicability of Immunocore's ImmTAC platform, potentially increasing the company's pipeline value. Investors should monitor upcoming Phase 2 and 3 trials, as positive results could significantly impact Immunocore's market valuation.
Immunocore presents Phase 1 data of brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with ovarian cancer
Brenetafusp is clinically active as monotherapy and in combination with chemotherapy in heavily pre-treated, platinum-resistant ovarian cancer patients
T cell fitness gene expression signature in blood is an important parameter of clinical activity for tebentafusp in uveal melanoma and for brenetafusp across different tumor types
(OXFORDSHIRE, England & CONSHOHOCKEN, Penn. & ROCKVILLE, Md., US, 14 September 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, today presented Phase 1 data with brenetafusp in patients with platinum resistant ovarian cancer at the 2024 European Society for Medical Oncology (ESMO) Congress. 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.
“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 2022. A majority of patients had received prior bevacizumab (
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
Thirty-one of the 37 monotherapy patients were evaluable for RECIST v1.1 tumor assessment,
Of the 29 monotherapy patients evaluable for circulating tumor DNA (ctDNA) response,
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 (
Phase 1 chemotherapy combination data in heavily pre-treated platinum resistant ovarian cancer patients
As presented today at ESMO 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 (
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 (
Eleven of the 16 combination patients were evaluable for ctDNA response. The molecular response rate was
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 (
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
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
Skin Reactions
Skin reactions, including rash, pruritus, and cutaneous edema occurred in
Elevated Liver Enzymes
Elevations in liver enzymes occurred in
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 (≥
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.
About Immunocore
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases, and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including nine active clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, 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.
Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding expected clinical benefits of ImmTAC molecules, including KIMMTRAK, brenetafusp, and the Immunocore’s other product candidates, including disease control, including partial responses, ctDNA molecular response, progression free survival and extended overall survival benefit, tumor reduction, and the potential to enhance clinical activity by increasing expression of the antigen presentation machinery in cancer cells; and expectations regarding the design, progress, timing, enrollment, randomization, scope, expansion, funding and results of the IMC-F106C-101 Phase 1/2 dose escalation trial with brenetafusp in patients with ovarian cancer. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions on the Company’s business, financial position, strategy and anticipated milestones, including Immunocore’s ability to conduct ongoing and planned clinical trials; Immunocore’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products, including as a result of health epidemics or pandemics, war in Ukraine, the conflict between Hamas and Israel, or global geopolitical tension; Immunocore’s ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes in inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict between Hamas and Israel, and global geopolitical tension; Immunocore’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of Immunocore’s current and future collaborations, partnerships or licensing arrangements, including the risk that Immunocore may not realize the anticipated benefits of its collaboration with Bristol Myers Squibb. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore’s filings with the Securities and Exchange Commission, including Immunocore’s most recent Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.
Contact Information
Immunocore
Sébastien Desprez, Head of Communications
T: +44 (0) 7458030732
E: sebastien.desprez@immunocore.com
Follow on Twitter: @Immunocore
Investor Relations
Clayton Robertson, Head of Investor Relations
T: +1 (215) 384-4781
E: ir@immunocore.com
1 Average based on Liu 2016, Lheureux 2021 & Griffiths 2011
FAQ
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