Merck and OncoSec expand Keytruda/IL-12 collaboration into triple-negative breast cancer

Merck and OncoSec Medical are partnering on a second clinical trial, this time combining two of their immunotherapies in metastatic triple-negative breast cancer, following a similar collaboration in melanoma announced last year.

The phase 2 trial will evaluate Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) and OncoSec’s ImmunoPulse IL-12 in patients with locally advanced and inoperable or metastatic disease, following the failure of systemic chemotherapy or an immunotherapy.

While checkpoint inhibitors such as Keytruda have extended progression-free and overall survival in certain cancers, many patients still do not respond to single-agent therapies alone. OncoSec predicts its IL-12, injected directly into the tumor, will help prime the body’s immune system and boost the general effectiveness of PD-1 therapies.

The growing class of dozens of PD-1, PD-L1 and related treatments have led to hundreds of oncology trials in recent years, as sponsors rush to test as many immunotherapy permutations as possible to find a successful, effective combination.

OncoSec will sponsor and fund the study while Merck will provide Keytruda, the two companies said in a statement. The two companies formed a similar agreement last May, for a phase 2 trial of the same drugs, with plans to enroll about 50 late-stage metastatic melanoma patients that progressed after an anti-PD-1 therapy. They expect to complete that trial by late 2020.

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Recently, a combination of Keytruda and Checkmate Pharmaceuticals’ CMP-001 was shown to reverse anti-PD1 drug resistance in advanced melanoma patients in a phase 1 study.

Checkmate’s small-molecule adjuvant aims to increase the expression of antigens within tumors to stimulate an immune system response. The study demonstrated a 22% objective response rate with strong durability, with some sustained for over six months.

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However, a trial of a different Keytruda combination—this time with Incyte’s IDO1 blocker epacadostat—was less fortunate. Phase 3 data released last month showed no benefits in progression-free survival compared to Keytruda alone, with little expectation that overall survival was going to succeed either.

Incyte halted the study, and would later decide to scrap its collection of late-phase epacadostat trials, including six testing combinations with Keytruda, as well as Bristol-Myers Squibb’s Opdivo (nivolumab) in head and neck cancer, renal cell carcinoma, urothelial cancer and non-small cell lung cancer. Two more pivotal trials were downgraded to phase 2 studies.

BMS itself ended two recently launched phase 3 trials last week, examining an IDO1 inhibitor it acquired through an $800 million deal with Flexus. The plug was pulled after recruiting just one of the 1,750 patients the company planned to enroll, citing changes in business objectives.