A New Generation of Cancer & Autoimmune Disease Treatment
Immunotherapy Clinical Trials.
AIPAC (ACTIVE IMMUNOTHERAPY PACLITAXEL)
Active Immunotherapy PAClitaxel (AIPAC) is Immutep’s most advanced and largest clinical trial. It is a Phase IIb clinical trial evaluating eftilagimod alpha (known as efti or IMP321) in combination with a taxane-based chemotherapy called paclitaxel in patients with hormone receptor positive metastatic breast cancer (MBC) as an immunotherapy. This combination treatment aims to boost the immune response against tumour cells compared to the chemotherapy treatment alone.
The study is taking place in Europe and consists of two parts: a safety run-in phase with 15 patients, which has now been completed, and a randomised and controlled phase which has fully recruited 227 patients.
Patients within the randomised and controlled phase of the study were placed into two different treatment groups: group A received paclitaxel chemotherapy in combination with a placebo, while treatment group B received paclitaxel chemotherapy in combination with efti. Thereafter, patients pass over to the maintenance phase.
AIPAC is a potentially pivotal trial, meaning subject to sufficient and clinically meaningful data and regulatory interactions, the final read-out of data could serve as a basis to pursue regulatory approval pathways for efti with the European Medicines Agency and the U.S. Food and Drug Administration.
TACTI-002 (Two ACTive IMMUNOTHERAPEUTICS)
Two ACTive Immunotherapies-002 (TACTI-002) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD’s KEYTRUDA® (or pembrolizumab, an anti-PD-1 therapy) for up to 183 patients.
The trial is a Phase II, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in up to 13 study centres across the U.S., Europe and Australia.
TACTI-002 evaluates the combination therapy in three types of patients:
- First line Non-Small Cell Lung Cancer (NSCLC) – known as Part A
- Second line NSCLC PD-X refractory – known as Part B
- Second line Head and Neck Squamous Cell Carcinoma – known as Part C
The study has an adaptive trial design called Simon’s two-stage. This allows the number of patients in each Part to be increased if a predefined number of positive results are observed in stage 1, creating a stage 2. Recruitment is ongoing.
For further information about the study, please visit:
TACTI-003 is a Phase IIb Clinical Trial in 1st line Head and Neck Cancer. Subject to ethical and regulatory approval, it will evaluate efti in combination with MSD’s KEYTRUDA® (pembrolizumab) as a first line therapy in unresectable recurrent or metastatic HNSCC patients with PD-L1 negative and PD-L1 positive (CPS ≥1) tumours. It will be a randomised, controlled clinical study in approximately 154 first line HNSCC patients and will take place across Australia, Europe and United States of America in up to 35 clinical sites.
The study will evaluate the safety and efficacy of efti in combination with pembrolizumab, compared to pembrolizumab alone in 1st line metastatic or recurrent HNSCC patients with PD-L1 positive (CPS ≥1) tumours (cohort A), and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumours (CPS <1) (cohort B). Approximately 130 patients in cohort A will be randomised 1:1 to receive either efti plus pembrolizumab or pembrolizumab alone. Subjects in cohort B (up to 24 patients) will receive a combination of efti and pembrolizumab.
The primary endpoint of the study is the Overall Response Rate (ORR) according to RECIST 1.1. iRECIST will be used for treatment decisions. Secondary endpoints include OS and Progression Free Survival (PFS). Following the grant of Fast Track designation for the combination of efti with pembrolizumab to treat 1st line HNSCC patients by the US FDA in early April 2021 and the appointment of a Contract Research Organisation (CRO), Immutep is on track to start the study in mid-2021.
TACTI-MEL (TWO ACTIVE IMMUNOTHERAPEUTICS IN MELANOMA)
Two ACTive Immunotherapeutics in melanoma (TACTI-mel) is a Phase I safety and dose finding clinical trial of efti given in combination with pembrolizumab (Keytruda) in patients with locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma. The study combined two immunotherapies to enhance the immune response by activated T cells.
Patients having a suboptimal response or having had disease progression with pembrolizumab as a monotherapy were eligible for the study and received the combination of pembrolizumab plus efti.
TACTI-mel took place in Australia and involved four cohorts of six patients, bringing the total number of patients in the trial to 24. The first three cohorts received ascending subcutaneous doses of efti up to 30 mg per injection in combination with pembrolizumab. The fourth cohort of six patients received 30 mg of efti in combination with pembrolizumab, starting at cycle one of pembrolizumab. All patients were treated for up to 12 months.
Safety data demonstrates that efti had a very favorable safety profile.
Final efficacy data from TACTI-mel showed that patients responded well to the combination treatment. Patients had an encouraging Overall Response Rates of 33% in Part A (where patients were dosed with efti at cycle 5 of prembrolizumab treatment) and 50% in Part B (where patients were dosed with efti from day 1 of cycle 1 of pembrolizumab).
This confirmed deep and durable responses to the combination treatment, meaning that patient tumours were shrinking and not growing back over a long follow up period. In addition, the study reported the complete disappearance of all target tumour lesions for a number of patients and one complete confirmed response where the tumour had completely disappeared.
INSIGHT-003 is an investigator-initiated trial conducted by the Institute of Clinical
Cancer Research IKF at Krankenhaus Nordwest in Frankfurt. It is being run as the third arm (Stratum C) of the ongoing Phase 1 INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator.
The trial is an expansion into triple combination therapy consisting of efti in conjunction with an existing approved standard of care combination of chemotherapy and anti-PD-1therapy.
Up to 20 patients with solid tumours will be recruited to participate in the trial. Patients will receive 30 mg subcutaneous doses of efti every two weeks in conjunction with standard of care chemotherapy plus anti-PD-1 therapy. The trial will assess the safety, tolerability and initial efficacy of the combination. The first interim results are expected in 2022.
For further information about the study, please see:
INSIGHT-004 is the 4th arm of the INSIGHT Phase I clinical trial. It is being conducted under lmmutep's clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc.
The trial evaluates the combination of efti with avelumab. a human anti-PD-L1 antibody, in 12 patients with advanced solid malignancies. It will assess the safety, tolerability and recommended Phase II dose of efti when combined with avelumab.
The Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH in Frankfurt, Germany (IKF) is the sponsor of the clinical trial and it will be conducted under the existing protocol of IKF's ongoing INSIGHT Phase I study.
At ASCO 2021, Immutep reported encouraging final data from its INSIGHT-004 arm (stratum D). Promising activity signals were demonstrated from the combination of efti and avelumab, with a response rate of 41.7% in patients with different solid tumours. In addition, deep and durable responses were seen in patients with low or no PD-L1 expression and in indications such as gastroesophageal and cervical cancer which typically do not respond to immune checkpoint therapy. Importantly, the combination therapy showed a good safety profile.
Please see below the poster:
For further information about the study, please see:
INSIGHT -005 is an amendment study to the protocol of the ongoing Phase I INSIGHT trial as the fifth arm (Stratum E). It is a Phase I/IIa clinical trial in patients with solid tumours.
The trial evaluates the feasibility, safety and efficacy of eftilagimod alpha, when given in combination with bintrafusp alfa (M7824), an investigational bifunctional fusion protein immunotherapy being jointly developed by Merck, Darmstadt, Germany and GlaxoSmithKline.
Bintrafusp alfa aims to block two immunosuppressive pathways, TGF-β and PD-L1, while efti activates antigen presenting cells, via the LAG-3 – MHC II pathway. Twelve patients are enrolled in up to two sites in Germany. The first data is expected to be delivered in 2022.