What to look out for at ASCO

This week, cancer patients, oncologists and investors alike look ahead to the annual meeting of the American Society of Clinical Oncology (ASCO), which kicks off in Chicago on Friday.

In the run-up to what is usually thought of as the world’s foremost cancer meeting, with speculation increasing over what new insights might be revealed by the global pharma and biotech industries, we read the runes to provide our take on what to look out for.

After a quieter-than-usual event in 2017, early signs indicate that this year’s ASCO – the American counterpart to the meeting of the European Society of Medical Oncology (ESMO) – will provide pointers towards a number of key, potentially game-changing clinical trends.

Plenary session

Perhaps the first place to look for headline-grabbing news is the plenary session. This year’s session highlights the following four programs.

“Early signs indicate that this year’s ASCO will provide pointers towards a number of key, potentially game-changing clinical trends.”

TAILORx

A Phase III trial of chemoendocrine therapy versus endocrine therapy alone in certain breast cancer patients.

Report from European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)

Looking at maintenance low-dose chemotherapy in patients with high-risk rhabdomyosarcoma, an aggressive and highly malignant form of cancer.

CARMENA

Results from a Phase III noninferiority study looking at cytoreductive nephrectomy followed by Sutent (sunitinib), versus Sutent alone in metastatic kidney cancer.

KEYNOTE-042

Keytruda (pembrolizumab) versus platinum-based chemotherapy as a first-line non-small cell lung cancer therapy.

Antibody-drug conjugates (ADC)

There is plenty of action on the ADC front this year.

There are currently two marketed ADCs, Adcetris (brentuximab vedotin), approved by the US Food and Drug Administration in 2011 and again in 2015, and Kadcyla (ado-trastuzumab emtansine), which has been marketed in the USA since 2013.

Adcetris developers Takeda Pharmaceutical (TYO: 4502) and Seattle Genetics (Nasdaq: SGEN) are still presenting positive Phase III data to build a case for the drug in Hodgkin’s lymphoma, although investors have been underwhelmed by its potential in this indication.

Roche’s (ROG: SIX) Kadcyla meanwhile has been successful in breast cancer, but has also struggled to gain the levels of reimbursement it requested in certain territories.

Immunomedics

Despite what might appear a thin record of success for this class of therapy, drugmakers are still plugging away, and there may be light at the end of the tunnel.

This year, many will be watching out for Phase I/II data from Immunomedics (Nasdaq: IMMU), related to its ADC candidate sacituzumab govitecan.

Activist shareholders scotched a deal, agreed around this time last year, for Seattle Genetics to gain rights to the therapy, which could be a challenger in  HR-positive/HER2-negative breast cancer.

Now going it alone, Immunomedics has taken longer to develop the candidate, only last week filing for regulatory approval in the USA. Nonetheless, markets have rewarded the firm with a near 200% increase in stock price for its efforts.

Other ADCs

Other firms to present data on ADCs this year include Astrazeneca (LSE: AZN), Immunogen (Nasdaq: IMGN), Menarini and Oxford Biotherapeutics.

Following on from the success of Kadcyla in breast cancer, Japanese pharma major Daiichi Sankyo (TYO: 4568), and fellow Tokyo-based firm Takeda (TYO: 4502) have results from their respective ADC candidates in this indication.

Daiichi is developing trastuzumab deruxtecan against HER2-positive breast cancer, and also U3-1402, another topoisomerase I inhibitor, against HER3-positive patients. Meanwhile Takeda and co-developer Mersana Therapeutics will offer data on XMT-1522.

Pfizer and AbbVie

AbbVie (NYSE: ABBV) and co-developer Pfizer (NYSE: PFE) will show overall response rate (ORR) and progression-free survival (PFS) data on cofetuzumab pelidotin, a PTK7-targeting ADC the firms believe has promise in various cancers.

For AbbVie, it could be the last chance to salvage some value from its $5.8 billion acquisitionof Stemcentryx, which the firm bought in 2016, largely to get its hands on leading ADC candidate Rova-T.

Extremely high hopes for Rova-T in lung cancer were dashed in dramatic fashion earlier this year, sending the Chicago native’s shares crashing.

While it’s probably too much to say the road to ADC success is littered with failures, there have been other high profile misses, including ADCT-502, which Switzerland’s ADC Therapeutics dropped in late April due to safety and tolerability issues.

It’s been a rough year for ADCs so far. For many of the firms mentioned here, ASCO 2018 could provide a platform to reinstil some hope for this approach.

I-O plus chemo combos

In recent months and years, there have been a slew of immuno-oncology trials, following on from the success of landmark checkpoint inhibitors and other immunomodulating therapies from Bristol-Myers Squibb (NYSE: BMY), Merck & Co (NYSE: MRK) and others.

Much of the recent activity has focused on combining established I-O therapies with chemotherapeutics, and data from ASCO 2018 look likely to enhance the potential for this therapeutic approach.

Merck has led the field here, with the first ever combo approval, and the firm has bet heavily on Keytruda (pembrolizumab), with billions invested in hundreds of trials.

Observers eagerly await results from the KEYNOTE-042 trial in lung cancer, to be presented at the plenary session, and will have to be patient until the curtain lifts to find out what the New Jersey-based firm has in store this year.

Merck is not the only one competing, however, with data from the CheckMate-227 trial to go on show, detailing that Bristol-Myers’ Opdivo (nivolumab) plus chemo reduced by 26% the relative risk of PFS, while results from a Roche (ROG: SIX) study will show impressive overall survival benefit.

Also look out for

Cemiplimab

Data from Regeneron Pharmaceuticals (Nasdaq: REGN) and Sanofi’s me-too checkpoint inhibitor cemiplimab. The firms are looking to offer the sixth therapy in this class, and have data showing a 47.5% response rate among certain patients.

The firms are hoping to show that blocking the PD-1 receptor is a better approach than stopping the PD-L1 ligand, as three of the current products on the market do.

Nerlynx (neratinib)

While Puma Biotechnology (Nasdaq: PBYI) has hit a rough patch in its regulatory efforts, the firm has data showing adjuvant use can improve invasive disease-free survival for some breast cancer patients. An exploratory analyses from the Phase III ExteNET trial provides useful learnings that may help to guide treatment practices to promote uptake.

https://bit.ly/2xDPPeP