Immutep Reports new positive interim data from its Phase II Study of LAG-3 candidate, Eftilagimod Alpha, in second-line PD-X refractory NSCLC

• ncouraging efficacy results continue for patients with 2nd line PD-X refractory non-small cell lung cancer (NSCLC)
• Patients in this 2nd line setting had confirmed disease progression on anti-PD-1 / anti-PD-L1 (“PD-X”) based first-line therapy[1]
• Key facts reported:

• Median Overall Survival (OS) from therapy with efti in combination with pembrolizumab is 9.7 months
• 25 percent were progression-free at 6 months and 36.5 percent were alive at 18 months[2]
• Chemo-free therapy of efti in combination with pembrolizumab continues to be safe and well tolerated, comparing favourably to standard of care chemotherapy-based options

Sydney, Australia, August 1, 2022 - Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”) a biotechnology company developing LAG-3-related immunotherapy treatments for cancer and autoimmune disease, is pleased to announce new interim data from second-line NSCLC patients (Part B) in the Phase II TACTI-002 trial. The data was presented as part of the electronic poster presentation at the IASLC 2022 World Conference of Lung Cancer (WCLC 2022) being held in Vienna, Austria and is also available on the Company's website.

This part of TACTI-002 (Part B), evaluates Immutep’s lead product candidate, eftilagimod alpha (“efti” or “IMP321”) in combination with MSD’s KEYTRUDA(R) (pembrolizumab) in a total of 36 patients with PD- X refractory metastatic NSCLC who were not pre-selected for their PD-L1 status. The data cut-off date is 1 July 2022.

In this second-line setting, patients were treated with pembrolizumab, which is an anti-PD-1 therapy, in combination with efti despite having confirmed disease progression on PD-X-based therapy in the first-line setting.[3] This was to evaluate whether efti with its unique mechanism of action in combination with pembrolizumab might provide a benefit for these patients that would otherwise move on to chemotherapy in the second line. Typically this standard of care second-line chemotherapy would be just single-agent taxane chemotherapy, as the majority of patients received platinum-based doublet chemotherapy plus chemotherapy plus PD-X therapy in the first-line setting. Thus, the enrolled patients were advanced in their disease with limited treatment options.

Immutep CSO and CMO, Dr Frederic Triebel, said: “It is encouraging to see efti in combination with pembrolizumab continues to report promising antitumour and safety results in second-line NSCLC. In particular, efti in combination with pembrolizumab is demonstrating sustained survival compared with standard of care chemotherapy regimens, and favourable safety and tolerability. Of course, for patients with such advanced disease, having a chemo-free alternative could mean a very real difference to their quality of life.”

“Furthermore, these results provide promising insights into how efti may provide a meaningful patient benefit in other PD-X refractory indications in the future,” he said.

TACTI-002 Investigator, Dr Martin Forster of the UCL Cancer Institute and University College London Hospital NHS Foundation, London, UK, said: "The TACTI-002 trial is showing 36.5 percent of patients have survived for at least 18 months when receiving efti in combination with pembrolizumab. The median overall survival is 9.7 months which is a meaningful survival benefit, plus disease control and durability have also continued favourably as the trial has advanced. All these results support further clinical investigation of efti in combination with pembrolizumab in PD-X resistant NSCLC patients".

Condition of Patients

All enrolled patients had confirmed progressive disease on or after standard of care first-line therapy with PD-X monotherapy (33 percent) or a combination of PD-X therapy and platinum-based doublet chemotherapy (67 percent). These patients are therefore resistant to PD-X-based therapy and are referred to as "PD-X refractory". Per standard clinical practice, they would otherwise usually go on to single-agent chemotherapy if they received combination with PD-X therapy and platinum-based doublet chemotherapy in first-line or, alternatively, go on to doublet chemotherapy if they received PD-X monotherapy in first-line. A vast majority (75 percent) of enrolled patients had a PD-L1 tumour proportion score (TPS) of less than 50 percent.

Accordingly, the enrolled patients represent a challenging to treat patient population with limited current treatment options.

Key Findings - data cut-off 1 July 2022

• Median OS of 9.7 months for those who received chemo-free therapy of efti in combination with pembrolizumab, which is comparable with current standard of care chemotherapy options in this second-line setting[4]
• Favourable sustained survival with 36.5 percent of patients alive at 18 months[5]
• Durable responses of 10+ months in 5.6 percent (2/36) of patients, with both patients continuing in the trial for over 11 months and 24+ months

Safety

Efti in combination with pembrolizumab continues to be safe and well-tolerated, with no new safety signals. Efti’s good safety profile to date compares favourably to the standard of care chemotherapy options.

Conclusion

Efti in combination with pembrolizumab is continuing to demonstrate encouraging early signs of antitumour activity in second-line confirmed PD-X refractory, NSCLC patients.

About the TACTI-002 Trial

TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck and Co., Inc., Rahway, NJ, USA (known as “MSD” outside the United States and Canada). The study is evaluating the combination of eftilagimod alpha (efti) with MSD’s KEYTRUDA(R) (pembrolizumab) in patients with second-line head and neck squamous cell carcinoma or non-small cell lung cancer in the first and second line.

The trial is a Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in study centres across Australia, Europe, and the US.

Patients participate in one of the following:

• Part A - first-line non-small cell lung cancer (NSCLC), PD-X naïve - given the promising results of the first two stages of Part A, an expansion stage with 74 additional patients was commenced in November 2020 to assist with trial design in subsequent late-stage settings
• Part B - second-line NSCLC, PD-X refractory
• Part C - second-line head and neck squamous cell carcinoma (HNSCC), PD-X naïve

TACTI-002 is an all-comer study in terms of PD-L1 status, a well-known predictive marker for response to pembrolizumab monotherapy especially in NSCLC and HNSCC.

More information about the trial can be found on Immutep’s website or on ClinicalTrials.gov (Identifier: NCT03625323).

[1] Disease progression was confirmed by two consecutive CT-scans at least four weeks apart, eliminating the possibility of pseudo- progressions.

[2] Calculated by Kaplan-Meier estimates

[3] Excluding any so called “pseudo-progressors”. A pseudo-progression refers to an increase in the apparent size of a tumour or number of metastases on an imaging test, that can falsely create the appearance of disease progression. This may be caused by the infiltration of immune cells into the tumour site or a delay in the development of an adaptive immune response following immunotherapy.

[4] Docetaxel and pemetrexed are approved by the FDA for treatment of 2nd line NSCLC: See Shepherd et al J Clin Oncol 2000 May 18(10):2095-103 and Hanna et al J Clin Oncol 2004 May 1;22(9):1589-97

which reported a median patient survival of 7 months and 8.3 months from treatment with docetaxel and pemetrexed, respectively, in second-line NSCLC.

[5] Compared to 15-25% with standard of care docetaxel chemotherapy (source CM-017; CM-057).

[6] As assessed by local investigator read.