Roche/BioNTech Report 'Low' Response Rate in Phase 1b Trial of Personalized Cancer Vaccine RO7198457 (BNT122)

Compiled by Keke

Recently, Roche and BioNTech presented the Phase 1b clinical results of their investigational personalized cancer vaccine RO7198457 (also known as BNT122) at the 2020 American Association for Cancer Research (AACR) Virtual Meeting. The data showed a “low” response rate to the vaccine, with 9 out of 108 evaluable patients with solid tumors responding when vaccinated and receiving combination therapy with Roche’s Tecentriq. Nevertheless, researchers pointed out that these immune response results support continued investigation in other patient populations.

This is a first-in-human Phase Ib clinical study evaluating RO7198457 in combination with the anti-PD-L1 antibody Tecentriq in patients with locally advanced or metastatic solid tumors. A total of 132 patients were enrolled to receive RO7198457 at doses ranging from 15 to 50 μg in combination with Tecentriq. RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered intravenously during the 12-week induction phase, with injections given weekly and then every other week; during the maintenance phase, injections were administered every 24 weeks. Tecentriq was administered at a dose of 1200 mg on Day 1 of each 21-day cycle.

The most common tumor types among enrolled patients were non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and colorectal cancer (CRC); the median number of prior treatments was 3 (range: 1–11); 39% of patients had previously received immunotherapy; the majority of patients had low PD-L1 expression levels (93% had PD-L1 expression <5% in tumor cells, and 79% had PD-L1 expression <5% in immune cells). The median number of RO7198457 injections administered to all patients was 8, and 16% of patients discontinued treatment due to Parkinson’s disease before completing the 6-week treatment period.

The data indicate that the majority of adverse events (AEs) were Grade 1–2. AEs with an incidence rate ≥15% included infusion-related reactions (IRR)/cytokine release syndrome (CRS), fatigue, nausea, and diarrhea. IRR/CRS were transient and reversible, primarily manifesting as Grade 1–2 chills and fever. No dose-limiting toxicities were observed. Seven patients discontinued treatment due to study drug-related adverse events.

RO7198457 induced the release of proinflammatory cytokines at each dose, consistent with the innate immune agonist activity of RNA. In vitro enzyme-linked immunospot (ELISPOT) assays and major histocompatibility complex (MHC) multimer analyses demonstrated RO7198457-induced neoantigen-specific T-cell responses in the peripheral blood of 37/49 (77%) patients. Up to 6% of MHC multimer-stained CD8+ T cells in peripheral blood exhibited a memory phenotype. RO7198457 induced T-cell responses against multiple neoantigens detected in post-treatment tumor biopsies. Among 108 patients who underwent at least one tumor assessment, 9 responded (objective response rate of 8%, including 1 complete response), and 53 had stable disease.

Source: Dr. Juanita Lopez & AACR.

It remains unclear whether these subjects will respond to Tecentriq monotherapy. Roche believes that the combination of RO7198457 and Tecentriq has a manageable safety profile, consistent with the mechanism of action of the investigational drugs, and induces significant levels of neoantigen-specific immune responses. Currently, a randomized Phase 1 clinical study evaluating RO7198457 in combination with Keytruda in patients with melanoma has commenced, and two randomized adjuvant therapy trials in patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) are planned.

Data from the smaller-scale Phase Ia clinical trial CT169 evaluating RO7198457 as monotherapy showed a response rate of 4% for this cancer vaccine; specifically, among the 26 patients who underwent at least one tumor assessment, one patient with gastric cancer responded (complete response lasting ≥10 months).

Roche’s Genentech paid BioNTech $310 million in upfront and milestone payments in 2016 to secure rights to develop mRNA-based personalized cancer vaccines. The two companies collaboratively developed RO7198457, a vaccine targeting 20 tumor-associated antigens (TAAs) expressed by patients’ cancers. The companies aim to elicit immune responses against tumors by delivering mRNA corresponding to these TAAs, thereby activating cytotoxic T lymphocytes and memory T cells.

Reference Source: Roche, BioNTech Post 'Low' Response Rate in Cancer Vaccine Trial