5016 - Lefitolimod vs standard of care (SOC) for patients with metastatic colorectal cancer (mCRC) responding to first-line standard treatment: Results from the randomized phase 3 IMPALA trial

Background

The TLR9 agonist lefitolimod broadly activates the innate and adaptive immune system. Based on encouraging data from the randomized phase II IMPACT trial, lefitolimod was evaluated in this phase III trial as switch maintenance treatment in patients with mCRC who have responded to first-line therapy.

Methods

The international, multicenter, open-label phase III IMPALA trial was conducted including the AIO, TTD and GERCOR cooperative groups and recruited 549 patients across 8 European countries. Patients who had an objective response to any standard first-line induction therapy (5FU/FA or CAPE, plus OX or IRI, alone or plus antiVEGF or antiEGFR) were randomized to receive either lefitolimod monotherapy (experimental arm) or local standard of care (control arm). After first progression, patients started re-induction therapy, with those in the experimental arm continuing lefitolimod on top.

Results

Demographics and baseline characteristics were well balanced between the study arms. Median duration of follow up was 35 months. The primary endpoint overall survival (OS) was not met: median OS was 22.0 and 21.9 months in the lefitolimod and control group, respectively (p = 0.2765; HR = 1.12; 95% CI 0.91 - 1.38). Progression free survival, event-free rates, pre-defined sub-group analyses including molecular and immunological parameters for OS did also not indicate a benefit. In comparison with the control arm treatment with lefitolimod was generally well tolerated. Rates of grade 3, 4 and 5 toxicities were 6.3, 1.9 and 0%, respectively and no new safety signals or autoimmune events were identified while immune activation was confirmed in peripheral blood.

Conclusions

Lefitolimod did not show superiority to standard of care as a single agent maintenance treatment in patients with mCRC. Limited add-on toxicity confirmed the favorable safety and tolerability profile of lefitolimod. Hence, and given its mode of action, lefitolimod will be evaluated in combination with other anti-cancer immunotherapies.

Clinical trial identification

NCT02077868.

Editorial acknowledgement

Legal entity responsible for the study

Mologen AG.

Funding

Mologen AG.

Disclosure

D. Cunningham: Advisory / Consultancy: Celgene; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Bayer; Advisory / Consultancy: 4SC; Advisory / Consultancy: Clovis; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Janssen; Advisory / Consultancy: Merck. R. Salazar: Advisory / Consultancy: VCN-BCN; Advisory / Consultancy: Agendia; Advisory / Consultancy: Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Roche Diagnostics; Advisory / Consultancy: Ferrer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Prizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Roche Farma; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: AZD; Speaker Bureau / Expert testimony: Celgene; Leadership role, Shareholder / Stockholder / Stock options: Sace Medhealth; Research grant / Funding (institution): Novartis Farmaceutica; Research grant / Funding (institution): PsiOxus Therapeutics Ltd; Research grant / Funding (institution): VCN Biosciences; Research grant / Funding (institution): Mologen. A. Sobrero: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. M.P. Ducreux: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Celgene; Research grant / Funding (self): Chugai; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Novartis; Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Spouse / Financial dependant: Sandoz. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. C. Tournigand: Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi. V. Molnar: Full / Part-time employment: Mologen AG. M. Starke: Full / Part-time employment: Mologen AG. M. Baumann: Leadership role: Mologen AG. E. Wiegert: Advisory / Consultancy: Mologen AG. M. Schmidt: Full / Part-time employment: Mologen AG. D. Arnold: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Amgen; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Terumo; Honoraria (self): Astellas; Honoraria (self): Biocompatibles; Honoraria (self), Advisory / Consultancy: Sirtex; Advisory / Consultancy: Boston Scientific; Honoraria (self): ArtTempi Media; Honoraria (self): PRiME Oncology; Honoraria (self): TRM Oncology; Advisory / Consultancy: IQVIA / Quintiles; Advisory / Consultancy: FlatIron. All other authors have declared no conflicts of interest.