Mining ASCO 2018's Gold, Part 11: The Pains In The Neck

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Includes: ESALY, EXEL, MRK, NVS, PFE
by: Zach Hartman

Summary

Today's edition focuses on the inches gained in the fight against head and neck cancer.

In particular, we see the interesting emergence of Novartis's PD-1 inhibitor.

TPT members got access to an exclusive discussion on an important AML drug.

Welcome to "Mining ASCO 2018's Gold," a series dedicated to helping you identify upcoming investment gems in biotech based on under-reported studies being presented at this year's big cancer meeting.

But first, did you happen to miss any of the previous editions? If so, please do give them a look!

Note: These articles come in groups of 4, but subscribers to the Total Pharma Tracker got an exclusive extra. So that's 10 potential investment ideas that you're missing out on if you are not a member. Join today for a free two-week trial!

Eisai and Merck collab shows signs of improved efficacy in head and neck

Abstract 6016 - A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with squamous cell carcinoma of the head and neck

Head and neck squamous cell carcinoma

Merck (MRK) and Eisai (OTCPK:ESALY)

Pembrolizumab is now an option for patients with head and neck squamous cell cancer, but to date this has not been a glowing area of success for the drug. Therefore, it is of great interest for MRK and patients alike to figure out how to enhance the benefit from pembrolizumab. And MRK has undertaken a shotgun approach, as evidence by this phase 1b/2 trial combining pembro and ESALY’s kinase inhibitor lenvatinib.

In all, 22 patients were enrolled in this study, with no preselection for PD-L1 status. Most of these patients had at least one prior line of therapy for their cancer. After median follow-up of 7.6 months, 36.4% of patients responded to the combination. Median duration of response and progression-free survival were both 8.2 months. If confirmed in a larger study, this would be a massive improvement over the 2.0 months observed in KEYNOTE-040 with pembrolizumab alone. Almost all of the patients experienced grade ≥3 adverse events, but only 4 of the patients discontinued therapy due to toxicity.

Overall, this study paints a nice early picture of a potentially valuable combination in this extremely difficult-to-treat form of cancer. However, I have to emphasize that these findings are too preliminary to make clear predictions, particularly when we’re talking about this level of toxicity.

Outlook: Neutral to positive

Pfizer scores a strong hit in phase 2 CDK4/6 inhibitor trial for head and neck

Abstract 6008 - Multicenter phase II trial of palbociclib, a selective cyclin dependent kinase (CDK) 4/6 inhibitor, and cetuximab in platinum-resistant HPV unrelated (-) recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC)

Head and neck squamous cell carcinoma

Pfizer (PFE)

It has been odd to watch the CDK4/6 inhibitors succeed so well in a specific form of breast cancer, and yet fail to make a big mark in other forms of cancer. Dysregulation in the Rb pathway is a common aberration that should make a lot of tumors amenable to treatment with these agents. Of course, the developers of these agents are still trying their darnedest, and PFE reported the findings of a phase 2 study involving the combination of the anti-EGFR antibody cetuximab with palbociclib in platinum-resistant head and neck cancer.

And as it turned out, there were some robust signs of efficacy with this combination. Of the 30 patients enrolled, 35% responded to the therapy, with 57% of the patients experiencing a decrease in the target lesion. The abstract divulged that the median overall survival (12.1 months) is the longest observed to date in the setting of platinum-resistant disease.

Clearly, this is a good sign for the CDK4/6 inhibitor in head and neck cancer. Could this be a near-term direction for PFE?

Outlook: Positive

Exelixis shows some activity for cabozantinib in thyroid cancer

Abstract 6088 - A phase II trial of cabozantinib (CABO) for the treatment of radioiodine (RAI)-refractory differentiated thyroid carcinoma (DTC) in the first-line setting

Thyroid cancer

Exelixis (EXEL)

Cabozantinib has come onto the oncology scene with a bang, garnering quick approvals and accolades in kidney cancer. However, in 2018 the drug has stalled somewhat in pursuit of groundbreaking activity in other indications. While effective, cabozantinib’s efficacy did not blow away shareholders in liver cancer.

But the work continues! EXEL presented a phase 2 study analyzing the use of cabozantinib in patients with radioiodine-refractory differentiated thyroid cancer. The trial enrolled 35 patients with a few different histologic subtypes of thyroid cancer. Over half (54%) of these patients achieved a partial response, with a median duration of response of 40 weeks. Another 43% of the patients had stable disease, which persisted for 25 weeks. True to form, cabozantinib was well tolerated, with toxicity being manageable with dose interruptions and adjustment.

Overall, these results are good for cabozantinib in this setting. Considering the dearth of treatment options in radioiodine-refractory disease, I expect that EXEL will enter into this space and become a competitor for ESALY’s lenvatinib.

Outlook: Positive

Remember Novartis’s PD-1 inhibitor? Me neither! But check out these thyroid cancer results

Abstract 6024 - Phase I/II study of spartalizumab (PDR001), an anti-PD1 mAb, in patients with anaplastic thyroid cancer

Anaplastic thyroid cancer

Novartis (NVS)

The immune checkpoint inhibitor space is complicated and crowded already, with 5 approved agents. But in the next year we have the potential to see 3 or 4 more from other big pharma agents. NVS is hoping to be a contender in this field with their own PD-1 inhibitor called spartalizumab. And an early target for them is anaplastic thyroid cancer, as part of a larger phase 1/2 study involving this agent in solid tumors. An early response in a patient with anaplastic thyroid cancer led to the opening of an expansion cohort enrolling 37 patients, most of whom had received prior therapy for their cancer.

30 of these patients were evaluable for efficacy, showing an overall response rate of 17.7%, and as of January 23, 2018, these responses were all ongoing. Another 10% of the patients achieved stable disease.

While it’s not much evidence, these findings are encouraging, even if the response rate is pretty low. It would appear as though the few patients who did respond have pretty durable remission. Considering no other immune checkpoint inhibitors are approved in this setting, it’s possible that this will be an early setting that NVS tackles as a landing site for spartalizumab.

Outlook: Positive

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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