Table of Contents

• Trial overview
• Colorectal cancer studies
• Skin cancer study
• Gastric cancer and gastrointestinal studies
• Basket and neoadjuvant studies
• Melanoma study
• Main endpoints and what they mean

Trial overview

These studies investigate Balstilimab in different cancer settings, usually as part of interventional trials, which means the researchers give a study treatment and then measure what happens.^{[1][2][3][4][5][6][7][8]}

The trial phases range from Phase 1 to Phase 3, so the program includes early safety studies, mid-stage activity studies, and a larger comparison study against standard treatment.^{[2][3][4][5][6][7][8]}

The main target groups are patients with advanced, metastatic, pretreated, or resectable cancers, and some studies focus on tumors with specific molecular features such as dMMR or MSI-H.^{[1][3][5][6][7]}

Colorectal cancer studies

One Phase 2 study, the UNICORN trial, is looking at short-course pre-operative targeted treatments in patients with molecularly selected and resectable primary colorectal cancer.^[1]

This study includes Balstilimab among several other drugs and is designed to see how well the treatment works before surgery.^[1]

The main outcome is the major pathological response rate, which means the share of patients whose removed tumor tissue shows either a complete response or a major response under central pathology review.^[1]

Another Phase 1 study combines Balstilimab with CR6086 in patients with pretreated mismatch-repair-proficient and microsatellite stable metastatic colorectal cancer, as well as other metastatic gastrointestinal cancers.^[4]

In this study, researchers are mainly checking safety, tolerability, and early signs of benefit, such as disease control rate and objective response rate.^[4]

A Phase 2 study also evaluates botensilimab with Balstilimab in refractory metastatic colorectal cancer.^[7]

The main endpoint is ORR, which measures how many patients have a complete or partial tumor response by RECIST 1.1 criteria.^[7]

Skin cancer study

A Phase 2 open-label study is testing Balstilimab alone in advanced or metastatic non-melanoma skin cancers.^[3]

The study includes advanced basal cell carcinoma that is not suitable for local therapy or has already progressed after at least one systemic treatment, as well as advanced squamous cell carcinoma and other skin cancers not suitable for local therapy.^[3]

The main endpoint is clinical benefit rate, which includes stable disease, partial response, or complete response.^[3]

Gastric cancer and gastrointestinal studies

A Phase 3 study compares botensilimab plus Balstilimab against standard treatment with FOLFOX/XELOX plus nivolumab in patients with locally advanced or metastatic MSI-H/dMMR gastric cancer.^[6]

The main outcome is overall survival, which means how long patients live after starting treatment.^[6]

Another Phase 1 study evaluates Balstilimab with CR6086 in pretreated mismatch-repair-proficient and microsatellite stable metastatic colorectal cancer, and the extension part includes other metastatic gastrointestinal cancers.^[4]

This study measures safety and early efficacy, including treatment-emergent adverse events, serious adverse events, and changes in lab tests, vital signs, performance status, ECG, and physical exam findings.^[4]

Basket and neoadjuvant studies

The NEOASIS Phase 2 basket study looks at immune checkpoint inhibition and other new immunotherapy combinations in several tumor types, including colorectal, esophageal, gastroesophageal junction, gastric, duodenal and small bowel, endometrial, breast, prostate, and sarcoma cancers.^[5]

The study includes both dMMR and pMMR tumors, and one of its goals is to test botensilimab plus Balstilimab before surgery.^[5]

Its main endpoint is major pathologic response, defined as less than 10% residual viable tumor in the surgical specimen, with a special response endpoint for a dMMR rectal cancer open cohort.^[5]

The UNICORN study also uses a pre-operative, or neoadjuvant, approach in resectable colorectal cancer, meaning treatment is given before surgery to improve the tumor response.^[1]

In some cohorts, the study also checks whether planned surgery can happen on time, which is important when researchers want to make sure treatment does not delay surgery too much.^[1]

Melanoma study

A completed Phase 2 study tested botensilimab as monotherapy and in combination with Balstilimab in advanced melanoma that did not respond to previous checkpoint inhibitor therapy.^[8]

The main endpoint was objective response rate, assessed using RECIST 1.1 criteria.^[8]

Main endpoints and what they mean

The trials use several different endpoints, depending on the cancer type and study phase.^{[1][3][4][5][6][7][8]}

• Safety and tolerability means the study checks how well patients can receive the treatment and what side effects or problems happen during the trial.^[2][4]

• DLTs, or dose-limiting toxicities, are side effects serious enough to limit treatment dosing.^[2][4]

• MTD, or maximum tolerated dose, is the highest dose that can be given without too many serious side effects.^[2]

• pCR means pathologic complete response, where no invasive cancer is found in the removed tissue.^[1]

• ORR measures how many patients have a complete or partial shrinkage of their tumors on scans or assessment.^[7][8]

• Overall survival measures how long patients live after treatment starts.^[6]