Part 3 Dose Decided for Botensilimab/Balstilimab in R/R MSS CRC

Agenus has accomplished an end-of-phase 2 assembly with the FDA concerning the investigation of botensilimab plus balstilimab for the therapy of sufferers with relapsed/refractory microsatellite secure (MSS) metastatic colorectal most cancers (mCRC) with out liver metastases, which included an settlement on the beneficial dose for a part 3 research.¹

The regulatory company and the corporate agreed on the proposed dosing of 75 mg of botensilimab as soon as each 6 weeks for as much as 4 doses plus 240 mg of balstilimab as soon as each 2 weeks for as much as 2 years. Notably, the FDA additionally beneficial the inclusion of a botensilimab monotherapy arm within the part 3 research on the discretion of Agenus.

Though information from a part 2 trial (NCT05608044) demonstrated that botensilimab plus balstilimab was lively in sufferers with relapsed/refractory MSS CRC, the FDA suggested towards submitting for accelerated approval of the mix because the goal response charges (ORRs) might not translate to a survival profit.

Interim topline information from the research confirmed that sufferers handled with the 75-mg dose of botensilimab plus balstilimab (n = 62) skilled an ORR of 19.4% (95% CI, 10.4%-31.4%). On this arm, the 6-month total survival (OS) fee was 90%.

In sufferers given the 150-mg dose of botensilimab plus balstilimab (n = 61), the ORR was 8.2% (95% CI, 2.7%-18.1%). Notably, botensilimab monotherapy given at 75 mg as soon as each 6 weeks (n = 38) and at 150 mg as soon as each 6 weeks (n = 40) elicited ORRs of 0% (95% CI, 0%-9.3%) and seven.5% (95% CI, 1.6%-20.4%), respectively. Within the standard-of-care (SOC) arm (n = 33), the ORR was 0% (95% CI, 0%-10.6%).

“Primarily based on the excessive stage of enthusiasm from vital numbers of worldwide scientific consultants and the promising scientific exercise we now have seen within the part 1 and a couple of research, our dedication to hunt all potential pathways to make botensilimab/balstilimab accessible to sufferers is unwavering,” Steven O’Day, MD, chief medical officer of Agenus, said in a information launch. “This consists of exploring alternatives to companion in america to perform a profitable part 3 trial.”

The part 2 information construct on beforehand reported information from a part 1 trial (NCT03860272), which confirmed that sufferers with refractory MSS mCRC who didn’t have lively liver metastases (n = 77) achieved an ORR of 23% at a median follow-up of 13.6 months Moreover, the median OS was 21.2 months, and the respective 6-, 12-, and 18-month OS charges had been 86%, 71%, and 62%.

Within the part 2, open-label, multicenter trial, investigators enrolled sufferers at the very least 18 years of age with unresectable and metastatic CRC adenocarcinoma whose tumors wanted to be assessed for microsatellite instability–excessive (MSI-H) or mismatch restore–poor (dMMR) standing. No less than 1 prior chemotherapy routine within the recurrent or metastatic setting was required. Different key inclusion standards consisted of measurable illness per RECIST 1.1 standards, a life expectancy of at the very least 12 weeks, an ECOG efficiency standing of 0 or 1, and enough organ perform.²

Sufferers with MSI-H or dMMR illness had been excluded. Different key exclusion standards included prior therapy with anti–PD-1, –PD-L1, or –CTLA-4 brokers; prior therapy with regorafenib (Stivarga) or trifluridine/tipiracil (TAS-102; Lonsurf); partial or full bowel obstruction inside 3 months of enrollment, signs of obstruction or radiological proof of impending obstruction; refractory ascites; and liver metastases.

Enrolled sufferers had been randomly assigned to obtain botensilimab plus balstilimab at 1 of two dose ranges; botensilimab monotherapy at 1 of two dose ranges; or SOC, which consisted of regorafenib or TAS-102.

ORR served because the trial’s main finish level. Secondary finish factors included period of response, progression-free survival, OS, security, and pharmacokinetics.

The mix’s security profile was manageable, and no new security alerts had been reported. Full topline information from the part 2 research shall be offered at an upcoming medical assembly.¹

“MSS CRC, representing roughly 95% of CRC circumstances, stays a illness setting with substantial unmet want and is taken into account to be one of the crucial difficult kinds of most cancers as a result of its excessive incidence and mortality charges,” Michael Sapienza, chief govt officer of Colorectal Most cancers Alliance, added in a information launch. “The quickly rising variety of diagnoses in youthful people is especially alarming. There may be an pressing want for brand spanking new therapy choices that may remodel the trajectory of MSS CRC and supply lasting advantages for sufferers.”

References

1. Agenus declares end-of-phase-2 assembly outcomes and topline interim part 2 information for BOT/BAL in MSS colorectal most cancers. Information launch. Agenus. July 18, 2024. Accessed July 18, 2024. https://investor.agenusbio.com/information/news-details/2024/Agenus-Declares-Finish-of-Part-2-Assembly-Outcomes-and-Topline-Interim-Part-2-Information-for-BOTBAL-in-MSS-Colorectal-Most cancers/default.aspx
2. A research of botensilimab and balstilimab for the therapy of colorectal most cancers. ClinicalTrials.gov. Up to date June 4, 2024. Accessed July 18, 2024. https://clinicaltrials.gov/research/NCT05608044