Anti-PD-1 data leads immuno-oncology buzz at ASH meeting

New data suggesting PD-1 inhibitors may have a role in haematological cancers as well as solid tumours headlined the American Society of Haematology (ASH) meeting in San Francisco over the weekend.

Phase I trials of Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co’s Keytruda (pembrolizumab) both showed impressive response rates in Hodgkin’s lymphoma, amid a series of other trials showing that immune-enhancing therapies can have a profound impact in blood cancers.

“For the past decade we have strived to leverage the immune system to fight resistant disease in extremely sick patients, so it is very encouraging that immunotherapies are now proving to be effective and relatively safe,” said Catherine Bollard of George Washington University at a press conference to highlight the new data.

BMS reported data from a study of 23 patients with Hodgkin’s lymphoma whose disease had progressed despite more than three previous treatment regimens, including Seattle Genetics’ Adcetris (brentuximab vedotin) and stem cell transplantation.

Giving Opdivo achieved a complete response in four patients and a partial response in a further 16, equivalent to an overall response rate of 87 per cent, and there were no life-threatening toxicities with the drug, according to the clinical investigators. The drug has been granted breakthrough status by the FDA on the strength of the Phase I data and a Phase II trial is now ongoing, according to BMS.

Meanwhile, a Phase I trial of Keytruda in a similar population of 29 patients revealed a 66% overall response rate, with six going into complete remission and 13 having a partial response. Once again, Keytruda was well-tolerated, according to the researchers behind the study.

While the PD-1 or ‘checkpoint’ inhibitors have shown promise in Hodgkin’s lymphoma, the jury is however still out on how effective they will be in other haematological malignancies.

Genetic analyses from the BMS study reported at ASH (and published in the New England Journal of Medicine) showed that all the patients exhibited a genetic mutation called 9p24.1 which seems to make their cancer particularly vulnerable to PD-1 blockade. Whether the drugs can show similar robust effects in other blood cancers remains to be seen.

BiTE back at leukaemia

Other highlights of the immuno-oncology track at ASH included a Phase II trial of Amgen’s just-approved Blincyto (blinatumomab) in acute lymphoblastic leukaemia (ALL).

Specifically, the trial enrolled B-cell ALL patients who had already responded to treatment but were shown to have residual traces of malignant cells in their bone marrow using a highly-specific new diagnostic test. These patients are at an elevated risk of relapse, notes Amgen.

In these patients, 78% of patients treated with Blincyto had a complete elimination of all residual disease cells – almost invariably after just one treatment cycle – and the patients will now be followed to see if this equates to a reduction in relapse risk.

Blincyto is the lead drug in Amgen’s bispecific T cell engager (BiTE) programme, which focuses on antibodies with two binding domains, one for the disease cell and the other for a patient’s immune cells.

“This is one of the first studies to evaluate a new compound in patients when they have trace amounts of residual disease, rather than when they are experiencing a full relapse,” said lead study author Nicola Gökbuget of Goethe University in Germany.

“Now that we are seeing promising results, we need to combine these strategies with others to better determine how to balance their potent anti-tumour activity with their potential toxicity to make them safer and even more effective,” said Bollard.

Anti-CD38 drugs coming through

New data on two anti-CD38 candidates – Genmab’s daratumumab and Sanofi’s SAR650984 – also attracted a lot of attention at ASH, with both drugs showing encouraging results in early-stage trials involving multiple myeloma patients.

A Phase Ib dose escalation study of SAR650984 in heavily pre-treated myeloma patients showed Sanofi’s drug achieved an average overall response rate of 55 per cent when given on top of standard therapy with lenalidomide and dexamethasone.

Meanwhile, a Phase I/II trial of daratumumab in combination with standard therapies for myeloma showed the drug did not add to the side-effect burden experienced by patients, while a Phase I trial found an overall response rate of 50 per cent in relapsed patients and 100 per cent in newly-diagnosed patients.

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