OncoSec Medical (ONCS) recently released interim results from its registration-enabled Phase 2B clinical trial in checkpoint-resistant metastatic melanoma patients. The market liked what it heard, and the stock is up appreciably since the release. In this article, I review the new data and provide other updates on developments that have occurred since my previous coverage.

(Source: BigCharts)

For company background, I recommend that readers peruse my first article, which was quite comprehensive. However, as a quick reminder, allow me to quote the section on ONCS’ approach vis-a-vis “hot” and “cold” tumors:

ONCS’ cancer treatment is intended to make “cold” tumors “hot” (explanation below) by injecting its pro-inflammatory cytokine IL-12 or Tavokinogene Telseplasmid, referred to simply as “TAVO”, into “cold” tumors and then using its electroporation technology to increase the permeability of the tumor cells’ membranes to get better uptake or distribution of the drug into the tumor. Once the tumors are “hot” they can be targeted by existing checkpoint inhibitors like Merck’s (MRK) Keytruda (chemical name Pembrolizumab) and Bristol-Myers Squibb’s (BMY) Opdivo (chemical name Nivolumab).

(Source: Enhancing Immunotherapy: The Race to Make “Cold” Tumors “Hot”, Dana-Farber Cancer Institute)

This brings us to the recent update on the company’s metastatic melanoma clinical trial.

KEYNOTE-695 Update

The KEYNOTE-695 study is a single-arm, phase 2, registration-enabled trial aimed at determining how well patients who failed prior checkpoint therapy in metastatic melanoma fare when treated with a combination of ONCS’ TAVO (aka IL-12) and Merck’s blockbuster Keytruda (aka pembrolizumab).

Here’s a slide summarizing the study and treatment protocol.

(Source: OncoSec November 2020 Presentation)

The primary efficacy endpoint for the study is 20% ORR (objective response rate) by standard RECIST (response and evaluation in solid tumors) criteria.

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The latest update included the following salient points:

  1. An ORR of 30% in the first 54 patients (i.e., in 16 of 54). Part of what gets the market excited here is that there are now enough patients to draw some statistical inferences, in particular that the 30% ORR has a 95% confidence interval ranging between 18% and 43.6%. Thus, the chances are quite high that the 20% bar will be met.
  2. Five out of 54 patients had 100% reduction of the targeted lesions (i.e., of lesions that were accessible to the ONCS electroporation device). I elaborate on this below.
  3. Median duration of response is 12.2 months, with many responding patients still on therapy (see below).
  4. Excellent safety profile. No grade 4 or 5 adverse events, and only 5.4% grade 3 treatment-related adverse events.

Let’s look at a few of these points in more detail.

100% Target Tumor Reduction

Nine percent of patients have a 100% reduction in their target lesions, and importantly, all 5 are still on study or follow-up. This latter point may help increase average duration of response.

The slide also highlights the fact that patients with prior exposure to ipilimumab (trade name Yervoy) had a 40% ORR.

(Source: OncoSec November 2020 Presentation)

One might be tempted to downplay this result, as it’s “only” 9%, but that would be neglecting the crucial point that these are patients who have failed all other therapies, and thus, they have no other alternatives. Looked at that way, reducing targeted tumors 100% in 9% of the patients is a great result.

Abscopal Effect

In patients who responded to treatment, all but one of the untreated lesions showed stable or reduced volume. This suggests that when a patient responds to ONCS’s treatment, it’s on a systemic immune system basis.

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(Source: OncoSec November 2020 Presentation)

Sustained Duration

The following slide shows that many of the responders are still responding and still on treatment or in follow-up one year into their treatment. For such seriously ill patients, this is an important accomplishment.

(Source: OncoSec November 2020 Presentation)

But metastatic cancer isn’t the only front on which ONCS is making great progress. There’s also:

KEYNOTE-890 in Triple-Negative Breast Cancer

Possibility of Moving Beyond Salvage Setting

In 2019, I wrote an article suggesting ONCS consider using biomarkers as a proxy for cold tumor sufferers who might benefit from early application of TAVO and Keytruda. Now. ONCS is doing something similar, adding a cohort to the KEYNOTE-890 study that will study the two drugs coupled with chemotherapy in first-line patients. Should this prove successful, it opens a much larger potential market to ONCS.

From the June 9th press release (with my emphasis):

[ONCS] today announced that, based upon tumor regression and associated clinical responses observed in the heavily pretreated Cohort 1 of the KEYNOTE-890 study, the Company plans to expand into earlier first-line treatment to investigate the combination of OncoSec’s lead product candidate TAVO™ (plasmid-based interleukin-12 or pIL-12) and Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy in patients with inoperable locally advanced or metastatic triple negative breast cancer (mTNBC). Cohort 2 will be added as a second arm to the ongoing KEYNOTE-890 study.

Merck’s Phase 3 KEYNOTE-355 trial evaluating KEYTRUDA in combination with chemotherapy in first-line mTNBC recently reported a statistically significant and clinically meaningful improvement in progression free survival (PFS) with the combination of KEYTRUDA plus chemotherapy versus chemotherapy alone for first-line treatment of patients with PD-L1 positive (CPS ≥10) mTNBC. Safety was consistent with known profiles of each regimen. These findings, as well as the strong signal, even in patients with PD-L1 negative tumors, and excellent safety profile observed in KEYNOTE-890 Cohort 1, served as the basis for OncoSec’s decision to move into first-line mTNBC.

Specifically, Cohort 2 of the KEYNOTE-890 study will evaluate the addition of TAVO in combination with KEYTRUDA and chemotherapy in the first-line setting in approximately 40 patients with mTNBC
. The primary endpoint will be overall responder rate (ORR) by blinded independent central review (BICR) based on RECIST v1.1. Should positive results from the KEYNOTE 890 Cohort 2 be observed, the Company plans to expand it and utilize the results from the expansion to seek accelerated approval.

(Source: OncoSec November 2020 Presentation)

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Valuation

ONCS continues to trade as a micro-cap, and as such, any positive results from either trial should re-rate the stock price substantially. I continue to be long a speculative position.

(Source: Seeking Alpha)

Disclosure: I am/we are long ONCS. 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.

Additional disclosure: I actively trade around core positions.



Via SeekingAlpha.com