On September 12, 2022 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of therapeutics designed to activate the immune response to cancers and infections, reported the initiation of a global Phase 2 program of botensilimab, an Fc-enhanced anti-CTLA-4 that activates innate and adaptive immune responses (Press release, Agenus, SEP 12, 2022, View Source [SID1234619445]). These trials include ACTIVATE-Colorectal, a Phase 2 study designed to evaluate botensilimab as monotherapy and in combination with balstilimab (anti-PD-1) for the treatment of microsatellite stable colorectal cancer (MSS CRC), and ACTIVATE-Melanoma, a Phase 2 study designed to evaluate botensilimab as a single agent for advanced melanoma, refractory to either prior anti-PD-1 or combined anti-PD-1/anti-CTLA-4 therapy. An additional Phase 2 study in pancreatic cancer is anticipated to begin later in 2022.
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"The Phase 1 botensilimab program demonstrated remarkable activity in poorly immunogenic and difficult to treat tumor types," said Steven O’Day, MD, Chief Medical Officer at Agenus. "In light of our compelling clinical data, we have received clearance from the FDA to initiate our Phase 2 development program in two indications and intend to expand to multiple additional indications as rapidly as possible with the aim of delivering a transformative new treatment option to patients in need."
ACTIVATE-Colorectal is a global, randomized, open-label, dose-optimization study evaluating the safety and efficacy of botensilimab as monotherapy and in combination with balstilimab in advanced refractory MSS CRC patients. Key elements of ACTIVATE-Colorectal include:
Patients must have received at least one prior chemotherapy regimen
Patients cannot have received prior PD-1, CTLA-4 or other immune checkpoint inhibitor therapy
Primary endpoint is overall response rate (ORR); secondary endpoints include duration of response (DOR), progression-free survival (PFS) and overall survival (OS)
Recruitment will be global, including sites in the United States and Europe
ACTIVATE-Melanoma is a global, randomized, open-label, multi-cohort, dose-optimization study evaluating the safety and efficacy of botensilimab as a single agent in advanced refractory melanoma. Key elements of ACTIVATE-Melanoma include:
Study will enroll patients who have failed prior anti-PD-1 therapy (cohort A) or both anti-PD1 and anti-CTLA-4 therapy (cohort B)
Primary endpoint is overall response rate (ORR); secondary endpoints include duration of response (DOR), progression-free survival (PFS) and overall survival (OS)
Recruitment will be global, including sites in the United States and Europe
About Microsatellite Stable Colorectal Cancer
Colorectal cancer remains the third most common cancer diagnosis and second-leading cause of cancer death worldwide, affecting 1.93 million and 916,000 individuals each year1. MSS colorectal cancer is a form of colorectal cancer where the cells’ DNA repair mechanisms remain intact2. It accounts for over 95% of metastatic colorectal cancer cases3 and has historically been unresponsive to immune checkpoint therapy4. Standard of care in pretreated metastatic MSS colorectal cancer offers limited benefit, with an approximate 1-2% response rate and a median of 6-7 months of survival5,6.
About Advanced Refractory Melanoma
Melanoma is a serious skin cancer that affects approximately 132,000 individuals each year and has been growing in incidence7. Advanced refractory melanoma refers to cancer that has spread to other parts of the body and stopped responding to medical therapy. Recent advances in the use of targeted therapy and immunotherapy, including anti-PD-1 and anti-CTLA-4, have improved survival for patients diagnosed with advanced melanoma. However, while anti-PD-1 monotherapy can be effective as a first-line treatment for some patients with metastatic melanoma, roughly half fail to achieve an objective response and those who do often subsequently relapse.8,9,10 Those patients with non-BRAF mutated tumors who are refractory to or who relapse after having received anti-PD-1 and anti-CTLA-4 therapy have few effective treatment options.
About Botensilimab
Botensilimab is a novel innate and adaptive immune activator that binds CTLA-4. The antibody was designed to enhance FcγR effector functions while avoiding complement-related toxicities and has demonstrated activity in cancer patients for whom current immuno-oncology agents have historically been ineffective. As presented at SITC (Free SITC Whitepaper) 2021, botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across nine cold and treatment-resistant cancers. At ESMO (Free ESMO Whitepaper) GI 2022, botensilimab demonstrated unprecedented activity in combination with balstilimab in MSS colorectal cancer, with a 24% response rate and 73% disease control rate in heavily pre-treated patients with a median of 4 prior lines of therapy.