On May 27, 2026 Callio Therapeutics, a biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment, reported that it will present a trial-in-progress poster highlighting the Phase 1 trial design of CLIO-8221 at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (May 29-June 2) in Chicago. CLIO-8221 is a first-in-class dual-payload ADC currently in Phase 1 clinical development (NCT07300943) for HER2-expressing solid tumors.
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"CLIO-8221 is the first program from Callio Therapeutics’ dual-payload ADC pipeline to enter the clinic, advancing our strategy to develop rationally designed payload combinations for hard-to-treat tumors," said Naomi Hunder, MD, Chief Medical Officer of Callio Therapeutics. "Developed with our proprietary linker technology and payload combination platform, CLIO-8221 is a first-in-class dual-payload ADC designed to deliver a topoisomerase 1 inhibitor and an ATR inhibitor directly to HER2-expressing tumors to address key mechanisms of resistance to existing HER2-targeted ADCs, including trastuzumab deruxtecan. With our Phase 1 trial now enrolling patients with advanced HER2-expressing solid tumors, we look forward to generating clinical data that will inform its potential as a differentiated treatment option."
"Patients with HER2-expressing solid tumors who progress on currently available HER2-targeted therapies continue to have limited treatment options," said Timothy A. Yap, MBBS, PhD, lead investigator at The University of Texas MD Anderson Cancer Center for the CLIO-8221 Phase 1 trial, and presenting author of the poster. "CLIO-8221 represents an innovative dual-payload approach to overcome resistance associated with existing HER2-targeted ADCs. This trial marks an important step in evaluating whether combining topoisomerase 1 and ATR inhibition within a single HER2-targeted ADC can expand treatment possibilities for patients with HER2-expressing solid tumors."
The Phase 1 clinical trial recruitment is ongoing in Australia and the United States, and the company plans to activate sites in China.
At ASCO (Free ASCO Whitepaper), Callio Therapeutics will present previously disclosed preclinical data (AACR 2026) that support the therapeutic potential of CLIO-8221 and the Phase 1 trial design:
By simultaneously delivering a topoisomerase 1 inhibitor (exatecan) and an ATR inhibitor (berzosertib), CLIO-8221 drives direct tumor cell killing at doses that also support a robust bystander effect, achieving superior in vivo efficacy compared to single-payload ADCs
CLIO-8221 demonstrated potent anti-tumor activity across varying HER2 expression levels and drove tumor regression after a single dose in both trastuzumab deruxtecan-sensitive and -insensitive models
CLIO-8221 exhibited a highly favorable safety profile; it was well-tolerated in non-human primates with no significant adverse effects observed at doses of 70 mg/kg (highest dose tested), establishing a No-Observed-Adverse-Effect Level (NOAEL) significantly higher than that of trastuzumab deruxtecan
Phase 1 of the study is a dose escalation with optional dose level expansions, and dose escalation may enroll across HER2-expressing cancers, including cancers that did not respond to or relapsed after trastuzumab deruxtecan treatment
Presentation details:
Poster/Abstract Title: Phase 1/2 Study of CLIO-8221, a HER2-targeted, dual-payload exatecan and ATR inhibitor antibody-drug conjugate (ADC) in patients with advanced HER2-expressing solid tumors
Poster Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date & Time: May 30, 2026, 1:30 PM – 4:30 PM CDT
Location: McCormick Place, Hall A – Posters and Exhibits
Presenter: Timothy A. Yap, MBBS, PhD, The University of Texas MD Anderson Cancer Center
Abstract Number: TPS3162
Poster Board: 295b
The full abstract is available on the ASCO (Free ASCO Whitepaper) Annual Meeting website. The poster will be available on the ASCO (Free ASCO Whitepaper) website on May 30, 2026.
About CLIO-8221
HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating meaningful benefit across tumor types, however, most patients eventually progress on treatment despite retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key reason for treatment failure. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, designed to address this challenge.
CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients who have progressed on existing HER2-targeted therapies.
(Press release, Callio Therapeutics, MAY 27, 2026, View Source [SID1234666133])