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Encouraging early data for Amgen’s BiTE therapies

Including first-in-man data from prostate cancer drug


Amgen has showcased some encouraging early stage data from candidates based on its novel bispecific T cell engager (BiTE) platform at ASCO.

Bispecific antibodies are one of the most promising emerging areas in immuno-oncology, with numerous biotechs and pharma companies developing their own variants of the technology. The potential is for the treatments to show superior efficacy to traditional antibodies, while having easier administration and fewer side-effects than CAR-Ts.

Amgen’s BiTEs work by attaching themselves to both a cancer cell and T cell, bringing them together so the body’s immune system can kill the cancer.

The company has more than a dozen BiTE molecules in clinical development across a range of haematological malignancies and solid tumours.

The most advanced of these is AMG 420, a candidate for patients with relapsed and/or refractory multiple myeloma (R/R MM), which has already caught attention with some promising early data at the ASH congress in December.

Analysts said that data suggested it could be a potential competitor with CAR-T treatments for multiple myeloma, most notably the Bluebird/Celgene frontrunner bb2121.

Amgen has presented new safety and efficacy results from its dose escalation trial which showed the drug was tolerable at the 400 µg/d dose, midway in the dosing range up to top end of 800 µg/d.

The updated readout showed that AMG 420 induced clinical responses in 13 of 42 patients across the dosing cohorts. Of the six patients that achieved a minimal residual disease (MRD)-negative complete response (CR), five were treated at the 400 µg/d dose. One patient achieved a very good partial response at this dose, and one achieved a partial response.

Overall, the results have led investigators to recommend further trials of AMG 420 to proceed at this 400 µg/d dose.

However as was seen when the study was presented in December, the immune-system stimulating treatment also produces relatively high levels of serious adverse events (AEs). These were reported in 19 patients (45%), with sixteen required hospitalisation and four needing prolonged hospitalisation.

No grade 3 or 4 central nervous system toxicities were observed but infections were seen in 13 patients, peripheral polyneuropathy in two patients and a Grade 3 cytokine release syndrome (CRS) was seen in one patient. If the BiTE technology is to mount a strong challenge to CAR-Ts, Amgen will want to demonstrate a superior safety profile to the cell therapies.

Analysts say it is too early to call on efficacy right now, as patients enrolled onto the AMG 420 trial have an average of four prior lines of therapy, while those treated in trials of Bluebird’s CAR-Ts had seven or more, with a slightly higher proportion of the latter group also failing on Johnson & Johnson’s fast-growing myeloma therapy Darzalex (daratumumab).

Amgen has FDA fast-track status for AMG 420, and intends to accelerate enrolment into an expanded study population that will include patients in earlier lines of therapy.

There were also initial results from a first-in-human trial of AMG 212 (pasotuxizumab)  in metastatic castration-resistant prostate cancer (mCRPC).

In the trial, 16 patients with mCRPC were enrolled into five dosing cohorts, with a target dose range of 5 to 80 µg/d delivered by continuous intravenous infusion.

AMG 212 showed clinical activity, a dose dependent response in key prostate cancer biomarker PSA, and two long-term responder patients.

Recruitment in the trial was stopped before maximum tolerated dose was reached to allow the set-up of a new Amgen-sponsored study.

Other BiTE’s in Amgen’s pipeline include AMG 596, which targets epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (GBM), and AMG 757, which targets delta-like ligand 3 (DLL3) in small-cell lung cancer (SCLC), with data presented on the candidates at ASCO poster sessions.

Article by
Andrew McConaghie

3rd June 2019

From: Research



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