Immutep’s Efti in Combination with MSD’s KEYTRUDA® Leads to Positive Efficacy with Favourable Safety in First Line Head and Neck Cancer
Immutep (ASX: IMM; NASDAQ: IMMP) announced positive results from the TACTI-003 Phase IIb trial evaluating eftilagimod alpha (efti) in combination with KEYTRUDA® for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. Key findings include:
1. Higher objective response rates (ORR) in patients with any PD-L1 expression (CPS ≥1): 32.8% for efti+KEYTRUDA vs 26.7% for KEYTRUDA alone.
2. Strongest outperformance in high PD-L1 expressing patients (CPS ≥20): 31.0% ORR (34.5% including post-cutoff data) vs 18.5% for KEYTRUDA alone.
3. High durability of response of 17.5 months in the combination arm.
4. Favorable safety profile with no new safety signals observed.
5. Statistically significant increase in absolute lymphocyte count, indicating efti's biological activity.
Immutep (ASX: IMM; NASDAQ: IMMP) ha annunciato risultati positivi dallo studio TACTI-003 Phase IIb che valuta eftilagimod alpha (efti) in combinazione con KEYTRUDA® per il trattamento di prima linea del carcinoma squamoso della testa e del collo ricorrente o metastatico. I risultati chiave includono:
1. Maggiore tasso di risposta obiettiva (ORR) nei pazienti con qualsiasi espressione di PD-L1 (CPS ≥1): 32,8% per efti+KEYTRUDA contro 26,7% per KEYTRUDA da solo.
2. Le migliori performance nei pazienti con alta espressione di PD-L1 (CPS ≥20): 31,0% di ORR (34,5% inclusi i dati post-cutoff) contro 18,5% per KEYTRUDA da solo.
3. Alta durata della risposta di 17,5 mesi nel braccio di combinazione.
4. Profilo di sicurezza favorevole senza nuovi segnali di sicurezza osservati.
5. Aumento statisticamente significativo nel numero assoluto di linfociti, indicativo dell'attività biologica di efti.
Immutep (ASX: IMM; NASDAQ: IMMP) anunció resultados positivos del ensayo TACTI-003 Phase IIb que evalúa eftilagimod alfa (efti) en combinación con KEYTRUDA® para el tratamiento de primera línea del carcinoma epidermoide de cabeza y cuello recurrente o metastásico. Los hallazgos clave incluyen:
1. Mayores tasas de respuesta objetiva (ORR) en pacientes con cualquier expresión de PD-L1 (CPS ≥1): 32.8% para efti+KEYTRUDA frente a 26.7% para KEYTRUDA solo.
2. Mejor desempeño en pacientes con alta expresión de PD-L1 (CPS ≥20): 31.0% ORR (34.5% incluyendo datos post-corte) frente a 18.5% para KEYTRUDA solo.
3. Alta durabilidad de respuesta de 17.5 meses en el grupo de combinación.
4. Perfil de seguridad favorable sin nuevos signos de seguridad observados.
5. Aumento estadísticamente significativo en el recuento absoluto de linfocitos, lo que indica la actividad biológica de efti.
Immutep (ASX: IMM; NASDAQ: IMMP)는 재발성 또는 전이성 두경부 편평세포암의 1차 치료를 위해 eftilagimod alpha (efti)와 KEYTRUDA®의 병용 요법에 대한 TACTI-003 2b상 시험에서 긍정적인 결과를 발표했습니다. 주요 결과는 다음과 같습니다:
1. 모든 PD-L1 발현 환자에서 더 높은 객관적 반응률 (ORR) (CPS ≥1): efti+KEYTRUDA의 경우 32.8% 대비 KEYTRUDA 단독의 경우 26.7%입니다.
2. PD-L1 발현이 높은 환자에서의 뛰어난 성과 (CPS ≥20): 31.0% ORR (전후 데이터 포함시 34.5%) 대비 KEYTRUDA 단독의 경우 18.5%입니다.
3. 병용 요법에서의 높은 응답 지속성 17.5개월.
4. 우호적인 안전성 프로파일과 새로운 안전 신호 없음.
5. 절대 림프구 수의 통계적으로 유의미한 증가는 efti의 생물학적 활성을 나타냅니다.
Immutep (ASX: IMM; NASDAQ: IMMP) a annoncé des résultats positifs de l'essai TACTI-003 Phase IIb évaluant eftilagimod alpha (efti) en association avec KEYTRUDA® pour le traitement de première ligne du carcinome à cellules squameuses de la tête et du cou récurrent ou métastatique. Les principales conclusions incluent :
1. Taux de réponse objective (ORR) plus élevé chez les patients ayant une expression de PD-L1 (CPS ≥1) : 32,8 % pour efti+KEYTRUDA contre 26,7 % pour KEYTRUDA seul.
2. Meilleure surperformance chez les patients expressant fortement PD-L1 (CPS ≥20) : 31,0 % d'ORR (34,5 % en incluant les données post-coupure) contre 18,5 % pour KEYTRUDA seul.
3. Durabilité élevée de la réponse de 17,5 mois dans le bras de combinaison.
4. Profil de sécurité favorable sans nouveaux signaux de sécurité observés.
5. Augmentation statistiquement significative du nombre absolu de lymphocytes, indiquant l'activité biologique d'efti.
Immutep (ASX: IMM; NASDAQ: IMMP) gab positive Ergebnisse aus der Phase IIb-Studie TACTI-003 bekannt, die eftilagimod alpha (efti) in Kombination mit KEYTRUDA® zur Erstlinientherapie von rezidiviertem oder metastasiertem Plattenepithelkarzinom im Kopf-Hals-Bereich evaluiert. Wichtige Ergebnisse umfassen:
1. Höhere objektive Reaktionsraten (ORR) bei Patienten mit jeglicher PD-L1-Expression (CPS ≥1): 32,8% für efti+KEYTRUDA gegenüber 26,7% für KEYTRUDA allein.
2. Die beste Überlegenheit bei Patienten mit hoher PD-L1-Expression (CPS ≥20): 31,0% ORR (34,5% einschließlich Daten nach dem Cut-off) gegenüber 18,5% für KEYTRUDA allein.
3. Hohe Haltbarkeit der Reaktion von 17,5 Monaten in der Kombinationsgruppe.
4. Positives Sicherheitsprofil ohne neue Sicherheitssignale.
5. Statistisch signifikante Erhöhung der absoluten Lymphozytenzahl, was auf die biologische Aktivität von efti hinweist.
- Higher objective response rates (ORR) in patients with any PD-L1 expression (CPS ≥1): 32.8% for efti+KEYTRUDA vs 26.7% for KEYTRUDA alone
- Strongest outperformance in high PD-L1 expressing patients (CPS ≥20): 31.0% ORR (34.5% including post-cutoff data) vs 18.5% for KEYTRUDA alone
- High durability of response of 17.5 months in the combination arm
- Favorable safety profile with no new safety signals observed
- Statistically significant increase in absolute lymphocyte count, indicating efti's biological activity
- High ORR (33.7%) and Disease Control Rate across all PD-L1 expression levels, including patients with negative PD-L1 expression
- None.
Insights
The results from the TACTI-003 Phase IIb trial are indeed promising for head and neck cancer treatment. The combination of eftilagimod alpha (efti) with KEYTRUDA® shows a 31.0% Objective Response Rate (ORR) in patients with high PD-L1 expression (CPS ≥20), compared to 18.5% ORR for KEYTRUDA® alone. This 1.9-fold increase in response rate is clinically significant.
Moreover, the 17.5-month median Duration of Response (DOR) for the combination therapy is impressive, especially when compared to the typical 6-7 month DOR seen with anti-PD-1 and chemotherapy combinations. This suggests a more durable benefit for patients.
The statistically significant increase in absolute lymphocyte count in the combination arm indicates efti's biological activity, potentially enhancing the immune response against cancer cells. Importantly, this improved efficacy doesn't come at the cost of increased toxicity, which is a common concern when combining therapies.
From an investment perspective, these results are highly encouraging for Immutep. The company's lead candidate, efti, is showing strong potential in a difficult-to-treat cancer type. The 1.9-fold increase in ORR for high PD-L1 expressors and efficacy across all PD-L1 expression levels could position efti as a valuable combination partner for checkpoint inhibitors.
The safety profile is particularly noteworthy. Unlike many combination therapies that improve efficacy at the cost of increased toxicity, efti maintains a favorable safety profile similar to KEYTRUDA® monotherapy. This could be a significant differentiator in the competitive immuno-oncology landscape.
Investors should watch for the Overall Survival data expected in 2025, as this will be important for regulatory discussions and potential commercialization. The company's engagement with regulatory authorities regarding potential paths forward is a positive step towards bringing this therapy to market.
The TACTI-003 trial results are clinically meaningful for head and neck cancer patients. The 34.5% ORR (including post-cutoff data) in high PD-L1 expressors (CPS ≥20) is a substantial improvement over KEYTRUDA® monotherapy. What's particularly intriguing is the efficacy across all PD-L1 expression levels, including PD-L1 negative patients.
The 17.5-month median DOR is impressive and could translate to improved long-term outcomes. The increased absolute lymphocyte count in the combination arm supports efti's mechanism of action in enhancing immune responses.
From a clinical perspective, the comparable safety profile to KEYTRUDA® monotherapy is crucial. This allows for potential long-term treatment without significantly increased toxicity burden on patients. If the Overall Survival data in 2025 aligns with these promising results, efti could become a valuable addition to our treatment arsenal for head and neck cancer patients.
- Results delivered in prestigious Proffered Paper oral presentation at ESMO Congress 2024
- In patients with any PD-L1 expression (CPS ≥1), efti in combination with KEYTRUDA outperformance is largest in CPS ≥20 with
31.0% ORR (34.5% ORR including partial response after data cut-off) versus18.5% ORR for KEYTRUDA - Efti in combination with KEYTRUDA led to a high durability of response of 17.5 months in patients with any PD-L1 expression and combination continues to have favourable safety profile
- Statistically significant increase in absolute lymphocyte count biomarker seen in the efti in combination with KEYTRUDA arm shows efti’s biological activity in a randomised setting
- Based on the high unmet need and encouraging results to date, with Overall Survival expected in 2025, the path forward will be discussed with regulatory agencies
SYDNEY, AUSTRALIA, Sept. 16, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces positive efficacy and safety results from the TACTI-003 Phase IIb trial evaluating eftilagimod alpha (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC).
These results with a data cut-off of 11 March 2024 were selected as a Proffered Paper oral presentation at the European Society for Medical Oncology (ESMO) Congress 2024 and were presented by Claus Kristensen, M.D., Ph.D., Head of Section for Thoracic and Head and Neck Oncology, Rigshospitalet, Copenhagen, Denmark, on 15 September. The data adds to the previously reported overall response rates and safety data on 27 June and 12 July.
Dr. Kristensen stated, "The efficacy and safety data in TACTI-003 are very encouraging and show the significant potential of this novel immunotherapy combination to fight difficult-to-treat head and neck squamous cell carcinomas. The clinically meaningful improvement in responses for patients with high PD-L1 expression in the randomised portion of the trial, combined with the compelling response rates in patients with no PD-L1 expression, are a testament to the complementary nature of efti in combination with KEYTRUDA. I am particularly impressed that these higher response rates and clear increase in biological activity seen in the efti arm do not come at the expense of durability of response or lead to an increased toxicity profile, which is often the case when combining therapies in the search for more efficacious treatments for cancer patients.”
Dr. Frédéric Triebel, CSO of Immutep, said “Through multiple clinical trials, we see the promise of efti to not only improve cancer patients’ clinical responses to immune checkpoint inhibitors, but also to expand patient populations who respond to them including patients with negative PD-L1 expression. Once again, the TACTI-003 trial has reinforced efti’s positive impact on both these fronts. We are excited to see efti in combination with KEYTRUDA now driving a 1.9-fold increase in responses for head and neck cancer patients with high PD-L1 expression as compared to KEYTRUDA alone, and a statistically significant increase in absolute lymphocyte count in the treatment arm showing efti’s biological activity in a randomised setting.”
Marc Voigt, CEO of Immutep, added “As we move into the latter half of 2024, we will continue to follow the data in TACTI-003 and start to engage with regulatory authorities regarding potential paths forward. We are certainly pleased with durability we are seeing, which is consistent with other trials in which efti combined with KEYTRUDA achieves a high DOR, unlike many other therapeutic combinations. We are hopeful this positive duration of response continues and, as seen in first line non-small cell lung cancer in the TACTI-002 trial evaluating efti in combination with KEYTRUDA, eventually contributes to an overall survival benefit for patients with first line head and neck cancer.”
ESMO Congress 2024 Proffered Paper Oral Presentation
Title: Primary Results from TACTI-003: A Randomized Phase IIb Trial Comparing Eftilagimod Alpha (soluble LAG-3) Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with CPS ≥1
Clinical Highlights from Randomised Cohort A in 1L HNSCC Patients with Any PD-L1 Expression (CPS ≥1)
Efti leads to higher Objective Response Rates (ORR)
- Efti in combination with pembrolizumab (E+P) led to a
32.8% ORR (34.5% including one partial response reported after data cut-off) in evaluable patients with CPS ≥1 (N=58) compared to26.7% for pembrolizumab in evaluable patients with CPS ≥1 (N=60), according to RECIST 1.1. Imbalances of prognostic markers towards the pembrolizumab alone arm included HPV status, smoking status, and primary tumour location. - E+P outperformance in patients with any PD-L1 expression was strongest in high PD-L1 expressing patients (CPS ≥20) with a
31.0% ORR (N=29) versus an18.5% ORR for pembrolizumab alone (N=27), along with a complete response rate of6.9% in E+P arm versus3.7% for pembrolizumab alone. An additional partial response was reported in CPS ≥20 after data cut-off leading to a34.5% ORR, a 1.9-fold increase in responses over pembrolizumab alone in this patient group.
Efti maintains a high Duration of Response (DOR)
- Durability of response was achieved with the addition of efti with a median DOR of 17.5 months in the E+P arm (N=58) as compared to 17.1 months in the pembrolizumab alone arm (N=60)
- Data compares favourably to other anti-PD-1 combinations with cytotoxic drugs like chemotherapy or EGFR inhibitors, including a historical DOR of ~6 to ~7 months from anti-PD-1 combined with chemotherapy in 1L HNSCC1-4
Efti increases Biological Activity
- A statistically significant increase in absolute lymphocyte count (ALC), measured as an exploratory biomarker, was seen in the E+P arm as shown in the graphic below, indicating an effective efti-induced immune response in this randomised setting
- ALC increase is in line with data from other Phase II trials evaluating efti in combination with chemotherapy in metastatic breast cancer or pembrolizumab in non-small cell lung cancer5-6
Efti continues to have favourable safety profile
- Efti in combination with pembrolizumab continues to have a favourable safety profile with no new safety signals observed
- Discontinuation rate from treatment emergent adverse events was similar for both E+P (
4.3% ) and for pembrolizumab alone (4.4% ) - Unlike other combinations with anti-PD-1 therapy, E+P continues to have a comparable safety profile to pembrolizumab alone other than injection site reactions as expected with efti’s subcutaneous delivery
- Discontinuation rate from treatment emergent adverse events was similar for both E+P (
Additionally, E+P drives a high ORR and Disease Control Rate (DCR) in 1L HNSCC patients regardless of PD-L1 expression. In Cohorts A and B together (N=89), E+P achieved a
This new data adds to the body of evidence that efti’s activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors (ICI) such as KEYTRUDA. As the only MHC Class II agonist in clinical development today, efti generates a broad anti-cancer immune response in combination with ICIs regardless of PD-L1 expression, including for patients with negative PD-L1 expression, in a unique and safe manner across multiple different cancers.
The ESMO Proferred Paper Oral Presentation slides are available on the Posters & Publications section of Immutep’s website.
Next Steps
Immutep will continue to follow the maturing data from TACTI-003, with the most relevant endpoint of Overall Survival expected in 2025, and engage with regulatory authorities regarding potential paths forward.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
About TACTI-003
The Two ACTive Immunotherapies-003 (TACTI-003) trial is an ongoing Phase IIb study (also known as KEYNOTE-C34) evaluating eftilagimod alpha (efti), Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with pembrolizumab as compared to pembrolizumab monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with pembrolizumab in patients with PD-L1 negative tumours (CPS <1).
The primary endpoint of the study is Objective Response Rate of evaluable patients according to RECIST 1.1. Secondary endpoints include Overall Survival, Objective Response Rate according to iRECIST, Progression Free Survival, and Duration of Response. For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).
About Immutep
Immutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com.
Australian Investors/Media:
Catherine Strong, Sodali & Co.
+61 (0)406 759 268; catherine.strong@sodali.com
U.S. Media:
Chris Basta, VP, Investor Relations and Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com
1 Cohen EEW et al. Lancet. 2019 Jan 12;393(10167):156-167. doi: 10.1016/S0140-6736(18)31999-8.
2 Burtness B et al. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7.
3 Haddad RI et al. J Clin Oncol. 2023 Apr 20;41(12):2166-2180. doi: 10.1200/JCO.22.00332.
4 Dzienis M et al. J Clin Oncol. 2024 Jul 22;42:2989-2999. doi: 10.1200/JCO.23.02625.
5 Wildiers H et al. Clin Cancer Res. 2024 Feb 1;30(3):532-541. doi: 10.1158/1078-0432.CCR-23-1173.
6 Forster M et al. Journal for ImmunoTherapy of Cancer 2023;11. doi: 10.1136/jitc-2023-SITC2023.0595.
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