As the masses begin to descend on Chicago, excitement for the 2018 ASCO annual meeting is palpable. This year’s theme of “Delivering Discoveries: Expanding the Reach of Precision Medicine” will draw more than 39,000 attendees from around the globe for what is sure to be an inspiring event.
To help you sift through the sheer volume of data due to be presented, we highlight select topics and abstracts that have grabbed the attention of our oncology experts here at Decision Resources Group.
Top trends to watch at ASCO:
- Spotlight on CAR T-Cell Therapies
- Immune Checkpoint Inhibitors in First-Line Metastatic NSCLC: It’s All About Combinations
- New Kids on the Immune Checkpoint Inhibitors Block
- IDO-1 Inhibitors: Data Reveal in Malignant Melanoma
- What Is The Potential of Nektar Therapeutics’ NKTR-214?
- IDH1/2 Inhibitors in AML
- Adjuvant Sutent in Renal Cell Carcinoma
- The Expanding Field of Oncology Biosimilars
With ASCO naming adoptive cell immunotherapy as the clinical cancer “Advance of the Year” in 2018, it is no surprise that the entire medical community is waiting with bated breath for the strong line-up of clinical data releases at this year’s ASCO meeting. Watch out for the following abstracts in this field:
- Multiple myeloma is the next frontier for CAR T-cell therapy in blood cancers, and a lot of excitement surrounds BCMA as a new target in this difficult-to-treat indication. Bluebird Bio and Celgene will present updated results for bb2121 in patients with relapsed/refractory multiple myeloma (abstract 8007). This anti-BCMA CAR T-cell therapy was granted FDA breakthrough therapy designation in November 2017.
- Kite Pharma, a Gilead company, will present durability of response data for Yescarta from the pivotal ZUMA-1 trial in refractory large B-cell lymphoma (abstract 3003) in addition to a sub-group analysis of outcomes by number of prior lines of therapy (abstract 3039).
- While lagging in the race of CD19-targeted CAR T cells, Juno Therapeutics’ (a Celgene company) will present updated data for lisocabtagene maraleucel from the TRANSCEND-NHL-001 trial (abstract 7505).
- Several other abstracts explore factors driving response to CAR T-cell therapy (abstracts 7567 and 7005) or the correlation between pre-CAR CD19 expression and outcomes (abstract 3051). Given the high price tag of CAR T-cell therapies, two abstracts looking at cost-effectiveness and social value of Kymriah in pediatric B-cell ALL also caught our attention (abstracts 10529 and 6610).
To gain insight in this field, look out for Decision Resources Group’s “Chimeric Antigen Receptor (CAR) T-Cell Therapy - Special Topics” report series. Get in touch for a custom market forecast of this exciting drug class.
Since 2015 and the market entry of immune checkpoint inhibitors for NSCLC, PD-1/PD-L1 inhibitors have taken center stage for this indication at every ASCO meeting. All eyes are now set on first-line combination regimens for metastatic NSCLC, a commercially lucrative setting.
- Last week, Merck & Co. announced that the Phase III KEYNOTE-407 met its co-primary end points of OS and PFS in an interim analysis. This trial evaluates Keytruda in combination with carboplatin plus paclitaxel or Abraxane plus paclitaxel as a frontline treatment for metastatic squamous NSCLC, regardless of PD-1 expression status—Merck & Co. will unveil the full much-awaited data at ASCO 2018 (abstract 105). These results may have an important impact on the treatment paradigm for metastatic squamous NSCLC, given that the currently approved combination of Keytruda plus Alimta and platinum is reserved for nonsquamous patients.
- At the plenary session, Merck & Co. will also present data from the Phase III KEYNOTE-042 trial, investigating single-agent Keytruda vs. standard platinum doublet chemotherapy in first-line metastatic NSCLC patients with 1% or higher tumor PD-L1 expression (abstract LBA4). We know that this trial met its primary end point of OS, a potentially practice-changing result that extends the relevance of Keytruda monotherapy beyond highly PD-L1-positive patients only (50% or greater tumor expression).
- Furthermore, Roche is also set to make strides at ASCO by rolling out PFS data from the Phase III IMpower 131 trial, which is assessing Tecentriq plus a chemotherapy doublet (carboplatin plus paclitaxel or Abraxane) as first-line treatment for metastatic squamous NSCLC (abstract LBA9000), and showing updated OS data from the Phase III IMpower150 trial of Tecentriq plus Avastin and chemotherapy in first-line metastatic nonsquamous NSCLC (abstract 9002).
Multiple industry-sponsored trials are assessing the potential of novel agents targeting the established immune checkpoints PD-1, PD-L1, and CTLA-4—as single-agents and as part of combination regimens—and this year’s ASCO meeting will offer a glimpse of this exciting clinical space.
- Data from early-phase studies of Regeneron/Sanofi’s PD-1 inhibitor cemiplimab in cutaneous squamous cell carcinoma (abstract 9519 and 9557) and in NSCLC (abstract e21057) will be presented.
- Novartis will present results from Phase I/II studies of its PD-1 inhibitor spartalizumab (PDR-001) as a monotherapy in anaplastic thyroid cancer (abstract 6024), in combination with LAG-525 (LAG-3 inhibitor) in advanced malignancies (abstract 3012), and in combination with lacnotuzumab (CSF-1 inhibitor) in advanced tumors (abstract 3014).
- Also watch out for early-phase data for Agenus’s AGEN1884 (a CTLA-4 inhibitor) and AGEN2034 (a PD-1 antagonist) in solid tumors (abstracts 3075 and 3086).
- CytomX Therapeutics will report first-in-human data for its PD-L1 targeting probody CX-072 in advanced solid tumors (abstract 3071).
- Finally, the designs of two Phase III trials of BeiGene’s PD-1 inhibitor tislelizumab will also be featured, the first in NSCLC (abstract TPS3112) and the second in hepatocellular carcinoma (abstract TPS3110).
In April 2018, Incyte and Merck rocked the oncology community by announcing the failure of the highly-watched Phase III ECHO-301/KEYNOTE-252 trial evaluating the IDO-1 inhibitor epacadostat plus Keytruda in unresectable or metastatic malignant melanoma.
Following this landmark event, Incyte downsized its clinical development program by terminating most of its pivotal IDO-1 trials, leading other developers (NewLink Genetics and BMS) to follow suit for their own IDO-1 assets. Results from the ECHO-301/KEYNOTE-252 study will be reported for the first time at ASCO 2018 (abstract 108).
Since news of the trial failure broke, physicians and researchers alike have been eager to understand why this once-promising combination stumbled in Phase III development. More than ten abstracts on epacadostat combination therapy are scheduled to be presented at ASCO 2018 across a multitude of indications.
Both NewLink Genetics and BMS are also scheduled to report preliminary findings from their IDO-1 inhibitor (indoximod and BMS-986205, respectively) trials. Collectively, these presentations will shed some light on IDO combinations, in the context of the frenzied development of combinatorial strategies that exploit checkpoint blockade in oncology.
In February 2018, BMS and Nektar announced a global development and commercialization collaboration for Nektar’s CD122 agonist NKTR-214—one of the most expensive deals to date.
But what has BMS betted on with this strategy? NKTR-214 has the ability to boost the immune system in patients lacking tumor infiltrating lymphocytes, which could potentially transform non-responders to PD-1 inhibitors (such as Opdivo) into responders.
Demonstrable efficacy in new patient populations could expand PD-1 inhibitor use across a wider range of oncology indications and fend off Opdivo’s main competitor Keytruda.
This year at the ASCO meeting, watch out for preliminary Phase I/II data for NKTR-214 plus Opdivo in advanced solid cancers (abstract 3006). Several posters will also provide a preclinical glimpse (abstracts 2567, 3085, 5582) into the potential of this highly anticipated agent.
In August 2017, Celgene and Agios Pharmaceuticals’ IDH2 inhibitor Idhifa (enasidenib) gained FDA approval for R/R AML patients with IDH2 mutation. The event was notable because Idhifa was granted full approval based on a single-arm Phase I/II (AG221-C-001) trial, thus becoming the first oral, targeted drug approved in the R/R setting.
- Earlier this year, the FDA granted priority review to Agios’s IDH1 inhibitor ivosidenib (AG-120) for IDH1-mutated R/R AML, based on data from the single-arm Phase I (AG120-C-001) study (the PDUFA date is set for August 21, 2018). Updated results from this study, also nominated a part of the “Best of ASCO” program, will be reported at this year’s ASCO meeting (abstract 7000).
- New clinical data from a fully enrolled ivosidenib arm of a Phase I/II trial combination trial of Idhifa or ivosidenib combined with Vidaza in previously untreated AML patients unfit to receive intensive chemotherapy will be unveiled for the first time (abstract 7042). Additionally, the design of the Phase III (AGILE) study exploring ivosidenib as an add-on therapy to Vidaza in newly diagnosed, IDH1-mutated AML patients ineligible for intensive chemotherapy will also be presented (abstract TPS7074).
In November 2017, the FDA approved a first-of-its-kind label expansion for the use of Pfizer’s Sutent to include the adjuvant treatment of renal cell carcinoma patients at high risk of recurrence postnephrectomy. This decision was based on a significant improvement in disease-free survival versus placebo in the Phase III S-TRAC study (abstract 4565).
Although many physicians have welcomed this new therapy in a setting where active surveillance has long been the only alternative, others have expressed concern about offering a pharmacological treatment with the potential for adverse events without a proven overall survival benefit. Furthermore, earlier this year in Europe, the CHMP recommended against expanding the use of Sutent into this setting—an opinion that Pfizer has since requested be re-examined.
With the final decision by the European Commission still pending, numerous ASCO abstracts are exploring the role of Sutent in the adjuvant setting, including two new meta-analyses of trials in this setting (abstracts 4567 and e16573), an immune cell signature that could act as a prognostic factor for disease-free survival (abstract 4562), and an analysis of patients’ perspectives on surveillance versus adjuvant therapy (abstract 4571).
This year’s ASCO annual meeting includes an oral session titled “The Arrival of Biosimilars”, where clinical data will be presented for biosimilars of three key oncology drugs, Roche/Genentech’s Herceptin, Rituxan, and Avastin.
The FDA labels for Herceptin, Rituxan, and Avastin encompass ten oncology indications, and therefore the emergence of biosimilars for these drugs is set to have a large impact on oncology markets.
While two oncology monoclonal antibody (MAb) biosimilars are currently FDA-approved (Amgen/Allergan’s Mvasi and Mylan’s Ogivri), they are yet to launch due to IP protection (Decision Resources Group anticipates the first oncology MAb biosimilars to launch in Q3 this year), and as such we expect the ensuing discussion around the emergence of these biosimilars in the United States (and other markets) to be particularly interesting.
This biosimilar session provides a good opportunity to learn more about major clinical outcomes of biosimilar bioequivalence to oncology branded biologics, and to gain insight into concerns and questions prescribers may have about oncology biosimilars.
Want to know more about biosimilars? Decision Resources Group covers this topic in-depth with dedicated biosimilars experts and solutions.
Decision Resources Group experts will be on the ground at the 2018 ASCO meeting to follow all of the exciting developments.
Follow #DRGOncology more thought leadership from the oncology team over the coming days!
Contributors: Marta Delgado, Ph.D., Joshua Dawkins, M.Pharmacol., Ph.D., Anamika Ghosh, Ph.D., Priti Girotra, M.Pharm., Ph.D., Aarushi Kashyap, M.Tech, Ann-Marie Looney, M.Sc., Ph.D, Swati Tyagi, M.Sc., MBA, , Jorrit Schafer, M.Sc., Ph.D, Khurram Nawaz, M.Sc