ASCO 2018 Preview – what to expect from this year’s conference

pharmaphorum will be presenting live online coverage of this year’s ASCO 2018 conference, the biggest event of the year for cancer medicine. Richard Staines presents a preview of the likely movers and shakers at the agenda-setting event.

Doctors, scientists and journalists are preparing for the yearly pilgrimage to Chicago to catch up on the latest results from advanced therapies at the American Society of Clinical Oncology (ASCO).

And it will be all the more exciting this year as a deepening knowledge of the biological mechanisms that cause the disease produces powerful therapies that can make a real difference to patients.

Cancer is one of the fastest moving areas of medicine, and the conference will showcase the cutting-edge therapies that could become available to patients in the coming years and could transform the fortunes of the companies that manufacture them.

ASCO 2018 is the conference where the next cancer blockbuster drugs emerge and is the most eagerly watched event for those who need a bellwether showing the latest trends in cancer research.

CAR-T data at ASCO 2018

Chimeric antigen receptor T-cell (CAR-T) therapies have been named by ASCO as the cancer advance of the year and there will be no shortage of data involving this revolutionary therapy.

Bluebird Bio will unveil updated phase 1 data from its bb2121 anti-BCMA CAR-T cell therapy,, which the company is developing in partnership with Celgene.

This therapy is targeted at B-cell maturation antigen (BCMA) and could offer an alternative therapy route in blood cancers such as multiple myeloma – already marketed CAR-Ts from Novartis and Gilead/Kite are aimed at CD-19.

The phase 1 data announced so far from bb2121 has been unexpectedly good in a heavily pre-treated patient population, with some even registering as minimal residual disease negative – less than one myeloma cell per million bone marrow cells.

This status is linked with lower relapse rates, and Bluebird and Celgene are looking to the phase 1 study to fine-tune a registration study known as KarMMA, in patients with relapsed/refractory multiple myeloma.

Celgene also owns the CAR-T biotech Juno Therapeutics outright and is due to announce data from the pivotal TRANSCEND trial of lisocabtagene maraleucel (JCAR017) in aggressive B-cell non-Hodgkin lymphoma.

Also known as JCAR017, the CAR-T therapy is the treatment that Juno Therapeutics switched to after a string of deaths in trials involving a different therapy.

Novartis will present an updated analysis of its JULIET pivotal phase 2 trial of Kymriah (tisagenlecleucel) in adult relapsed or refractory patients with diffuse large-B cell lymphoma (DLBCL).

There will also be data from two trials in young adults with acute lymphoblastic leukemia (ALL), and a presentation on the experience in US commercial manufacturing of the drug for use in ALL patients.

Combination oncology therapies

One notable trend is to use chemotherapy in combination to enhance the efficacy of an immunotherapy such as a checkpoint inhibitor.

Roche will be presenting new progression-free survival figures from its phase 3 IMpower131 study of its PD-L1 checkpoint immunotherapy Tecentriq, plus carboplatin and nab-paclitaxel chemotherapy, in first-line non-small cell lung cancer (NSCLC), a hotly contested and valuable indication for pharma.

There will also be new overall survival data in Tecentriq (atezolizumab), plus Avastin (bevacizumab) and chemotherapy (carboplatin and paclitaxel) in untreated non-small cell lung carcinoma (NSCLC).

Another example of a company developing a chemo-immunotherapy combination is Exelixis, which is already hoping to compete with Bristol-Myers Squibb’s PD-1 checkpoint inhibitor Opdivo (nivolumab) as a monotherapy in diseases such as kidney cancer, with its oral chemotherapy drug cabozantinib.

Cabozantinib is already launched in Europe and marketed by Exelixis’ partner Ipsen under the brand name Cabometyx, where it is taking on the might of Bristol-Myers Squibb’s Opdivo (nivolumab) in kidney cancer.

But the San Francisco biotech is also exploring Cabometyx’s use as a combination therapy with Opdivo.

One of the highlights of its 15 presentations at ASCO will be an early stage trial in combination with Opdivo, with or without Yervoy (ipilimumab), in metastatic genitourinary cancers.

Exelixis is also combining Cabometyx with Opdivo and Pfizer’s established chemotherapy Sutent (sunitinib) in first-line advanced or metastatic renal cell carcinoma.

The company said there will be a poster presentation from the CheckMate 9ER trial testing this combination in kidney cancer at the conference.

First-line lung cancer data

First-line lung cancer is a hotly contested indication, worth billions of dollars to pharma companies that are now competing to produce ever more effective combinations, or those that cover the range of mutations that the disease can express.

BMS’ Opdivo has failed to make an impact in the lucrative first-line non-small cell lung cancer use as a monotherapy – but BMS hopes to rectify this with a first analysis from its phase 3 CheckMate-227 trial.

Merck’s Keytruda (pembrolizumab) is the leader in this use, but BMS is testing Opdivo, with chemotherapy and its CTLA4 inhibitor Yervoy in first-line NSCLC.

The patient group tested has low levels of the biomarker PD-L1, a hurdle that Opdivo has so far struggled to clear.

Eisai and Merck & Co. at ASCO 2018

Eisai is testing its cancer drug lenvatinib in combination with Merck’s Keytruda and the Japanese pharma will present data from trials of lenvatinib, marketed as monotherapy under the brand name Lenvima, in multiple cancer tumours.

Merck and Eisai signed a potential $5.76billion R&D tie-up around lenvatinib and Keytruda back in March and the first data is due to be unveiled at ASCO 2018.

The firm is expected to share data on lenvatinib in combination with Keytruda in multiple types of cancer, including liver, kidney, endometrial and head and neck cancers.

It’s not just chemotherapy that is being used in combination with immunotherapies. Nektar Therapeutics is testing a CD122-biased agonist in combination with Opdivo.

Nektar’s NKTR-214 has been developed in a partnership with BMS that explores the possibility of combining drugs that stimulate natural killer cells, to augment an attack from the T-cells activated by the checkpoint inhibitor.

Small molecules

Small molecule drugs are still very much part of cancer care, as they can be made into patient-friendly pill formulations unlike antibody drugs, which are injected or infused into the blood stream.

Tesaro is one of several companies to have brought a poly ADP-ribose polymerase (PARP) inhibitor class drug to the market.

The biotech will give an oral presentation of data from a combination of its Zejula (niraparib) inhibitor and an anti-PD-1 in patients’ triple-negative breast cancer or recurrent ovarian cancer, and a poster presentation of data from the QAUDRA advanced ovarian cancer trial.

Winners and losers

Some definite winners and losers have already emerged from the first round of abstract publications.

Shares in the biotech Loxo Oncology soared by as much as 18% thanks to some impressive data from its LOXO-292 in a small group of patients with rearranged during transfection (RET) mutation.

Jounce Therapeutics is trying to find other immunotherapies to combine with checkpoint inhibitors.

But shares in the biotech crashed after some disappointing response rates in gastric cancer from the phase 1/2 ICONIC trial of its JTX-2011 announced ahead of the conference.

As monotherapy only one out of seven patients responded, and two out of 19 responded who got it in combination with Opdivo. Shares plunged by as much as 26% following the results.

Preclinical data suggests a dual mechanism of action stimulating T-effector cells and reducing the immunosuppressive regulatory T cells near tumours.

ICONIC tests JTX-2011 as monotherapy and in combination with Opdivo in four solid tumour types – gastric cancer, triple negative breast cancer, head and neck squamous cell cancer and non-small cell lung cancer, with patients completing at least one efficacy assessment.

Celgene, which has a collaboration with Jounce over JTX-2011, will be watching closely.

There’s bound to be more surprises, good and bad, in the build-up to the conference, and as late-breaking research is announced at the event itself.

Immunotherapies in particular can be unpredictable and have produced as many disappointing results as they have jaw-dropping improvements in survival.

So keep watching this space and let the drama unfold with pharmaphorum’s exclusive coverage.

Deep Dive oncology special published at the end of June, this special report combines analysis and insight from ASCO 2018 with a look ahead to ESMO and a series of exclusive, future focussed articles from key industry expertshttps://pharmaphorum.com/deep_dive/