Gritstone Oncology is advancing its investigational immunotherapy Slate into Phase 1 clinical studies sooner than planned, and expects patient enrollment to start as early as mid-2019, the company announced.
This follows feedback from the U.S. Food and Drug Administration (FDA), which will review toxicity data from Granite — another therapy from Gritstone that uses the same viral vector — to support Slate’s investigational new drug (IND) application.
Because Slate and Granite share the same delivery system, they are expected to have similar toxicity profiles in preclinical studies. Also, the two therapies were designed to target common patient populations and have similar manufacturing protocols.
This means that Gritstone no longer will need to conduct additional preclinical studies with Slate to explore its safety and toxicity, and can anticipate the filing of the IND with the FDA in approximately six months.
If the regulatory agency approves Slate’s IND, the company is planning to launch a Phase 1 trial to assess its safety and effectiveness, in combination with immune checkpoint inhibitors, for the treatment of advanced solid tumors.
“Following our recent FDA interactions, we are expecting to open the SLATE Phase 1 study to patient enrollment as early as mid-2019, which is substantially faster than we had forecasted,” Andrew Allen, MD, PhD, said in a press release. Allen is co-founder, president, and CEO of Gritstone Oncology.
Slate and Granite are both being developed to elicit strong immune responses against tumor-specific neoantigens — proteins unique to tumor cells that arise from mutations the tumor’s DNA and can be targeted by the patient’s own immune system.
According to Gritstone, “neoantigens can be classified as either patient-specific, meaning each patient has their own unique neoantigens, or shared, in which common driver mutations are found across some patients.”
So, while Granite is a personalized treatment — in which a patient’s specific neoantigens are included in a viral-based vector to activate the immune system — Slate is meant to treat several patients across multiple tumor types, including shared neoantigens.
Slate is being developed as an off-the-shelf immunotherapy and is believed to be suitable to treat approximately 12-13% of patients with colorectal and non-small cell lung cancer, and almost 30% of patients with pancreatic cancer.
Both Slate and Granite “use the same immunogenic viral vector system to deliver tumor-specific neoantigens (TSNA) to patients with the objective of driving a powerful and sustained T-cell response against their own tumors,” Allen said.
Slate is “designed for the subset of patients whose tumors carry specific oncogenic driver mutations resulting in neoantigens that are common across certain tumor types and patients,” Allen explained. Slate “unites the expected potency of a TSNA-directed immunotherapy with the convenience of an ‘off-the-shelf’ product.”
Granite is already being explored in a Phase 1/2 clinical trial (NCT03639714) in combination with checkpoint inhibitors in patients with lung cancer, colorectal cancer, gastroesophageal cancer, and bladder cancer, among others. The trial is recruiting participants at four sites in the U.S.
Slate’s Phase 1 trial is expected to include patients with metastatic lung cancer, pancreatic cancer and colorectal cancer, as well as patients with other solid tumors that carry specific genetic profiles.
The company is already applying for a screening protocol for recruiting eligible participants for Granite clinical studies at multiple sites. The same strategy will be applied to advance Slate’s clinical studies and enable early identification of eligible participants.
Preliminary results from the first part of both Slate and Granite trials are expected by year’s end.