Immutep Limited provided an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 March 2024. The TACTI-002 trial is ongoing with Immutep continuing to follow patients with 1L NSCLC (Part A) where, encouragingly, a median Overall Survival has not yet been reached in patients with high PD-L1 expression (TPS =50%). As previously reported at ESMO 2023, excellent median Overall Survival rates were seen across all levels of PD-L1 expression, including in patients expressing any PD-L1 (patients with a Tumor Proportion Score [TPS] of >1%) and patients with low PD-L1 expression (TPS 1-49%), with 35.5 months and 23.4 months reported respectively.

Immutep has previously reported final data from Parts B and C of the TACTI-002 trial. The TACTI-003 multicenter Phase IIb trial evaluating efti in combination with MSD?s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) is ongoing with a total of 171 first line head and neck squamous cell carcinoma (1L HNSCC) patients enrolled. Cohort A evaluating efti in combination with KEYTRUDA® as compared to KEYTRUDA® monotherapy (randomised) involves 138 patients with PD-L1 positive (Combined Positive Score [CPS] =1) tumours and Cohort B (non-randomised) includes 33 patients with PD-L1 negative tumours.

Subsequent to quarter end Immutep announced positive preliminary topline results from Cohort B. The investigational immuno-oncology combination demonstrates an overall response rate (ORR) of 26.9% and disease control rate (DCR) of 57.7% in 26 evaluable patients whose tumours do not express PD-L1 (CPS<1), according to RECIST 1.1, which compares favourably to historical controls. The final number of evaluable patients in Cohort B is expected to be higher and additional data, including complete response rate, is expected to be released together with Cohort A data. Data collection, cleaning, and analysis continue for TACTI-003, and the Company expects to report the primary endpoint (overall response rate according to RECIST1.1) from Cohorts A & B in H1 CY2024.

Immutep announced the first clinical data from the 90mg dosing of efti, the dose ever administered to patients, from patients participating in the safety lead-in of the AIPAC-003 trial in metastatic breast cancer (MBC). Data from the six patients in the safety lead-in showed the 90mg dose of efti in combination with paclitaxel is safe and well tolerated. The initial efficacy data was also encouraging, with a 50% overall response rate, including one patient reporting a complete response (complete disappearance of all lesions), and a 100% disease control rate.

The trial has proceeded to the randomised Phase II portion of study consisting of up to 58 evaluable patients who will receive 30mg efti or 90mg efti to determine the optimal biological dose of efti in combination with paclitaxel. Currently, 34 patients have been dosed in the randomised part. Further updates from AIPAC-003 will be provided in CY2024.

The investigator-initiated INSIGHT-003 trial continued to enrol patients throughout the quarter, with 38 out of a total of 50 patients enrolled and safely dosed across six sites in Germany. INSIGHT-003 evaluates a triple combination therapy consisting of efti and an approved standard of care combination of chemotherapy (carboplatin and pemetrexed) and anti-PD-1 therapy (pembrolizumab) in patients as first line treatment in non-squamous NSCLC adenocarcinomas. The first patient in the investigator-initiated INSIGHT-005 trial was enrolled and safely dosed, as announced in January 2024.

The study is evaluating efti and the anti-PD-L1 therapy BAVENCIO® (avelumab) in up to 30 patients with metastatic urothelial cancer and is jointly funded with Merck KGaA, Darmstadt, Germany. The investigator-initiated EFTISARC-NEO trial is ongoing with 14 patients now enrolled and safely dosed. The study evaluates efti in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting.

IMP761 is the Company?s proprietary preclinical candidate and world?s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. Throughout the quarter, Immutep progressed its pre-clinical development and IND-enabling toxicology studies for IMP761 to evaluate the safety and toxicity of its product candidate before entering first-in-human trials.