Targeted drug shrinks hard-to-treat ovarian tumors, early data show
Context says data from Phase 1 trial indicate CTIM-76 well tolerated
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Weekly treatment with Context Therapeutics’ CTIM-76 was generally well tolerated and shrank tumors in some people with heavily pretreated platinum-resistant ovarian cancer, according to first interim data from an ongoing Phase 1 clinical trial.
The ongoing Phase 1 trial (NCT06515613), currently recruiting at sites in the U.S. and the U.K, is evaluating CTIM-76 in up to 156 adults with platinum-resistant ovarian cancer and other solid tumors. Interim findings come from the Phase 1a, or dose-escalation, portion of the study, which is assessing the therapy’s safety and antitumor activity while helping identify the doses and dosing schedules that will be carried forward into the Phase 1b expansion phase.
“In our first clinical presentation of dose-escalation data, weekly administration of CTIM-76 produced compelling anti-tumor activity and a well-tolerated safety profile in heavily pretreated patients,” Martin Lehr, Context’s CEO, said in a company press release. “Building on this encouraging data, we have advanced into the next phase of development, where we will evaluate CTIM-76 administered every three weeks.”
Platinum-resistant ovarian cancer occurs when a tumor no longer responds to platinum-based chemotherapy, the standard first-line treatment for ovarian cancer. In such cases, treatment options are limited, and outcomes are generally poor.
CTIM-76 is a bispecific antibody designed to simultaneously recognize and bind CD3, a protein found on T cells, and CLDN6, a protein present on the surface of several cancers, including ovarian, endometrial, and testicular tumors, but largely absent from healthy adult tissues. By linking T cells to cancer cells expressing CLDN6, the therapy is intended to direct the immune system to attack the tumor.
Evaluating safety after promising preclinical results
In preclinical studies, CTIM-76 demonstrated potent and selective activity against CLDN6-expressing cancer cells and induced dose-dependent tumor regressions in animal models, while remaining well tolerated, according to Context.
In the Phase 1a portion, participants receive one of nine escalating doses of CTIM-76 once weekly over a 28-day treatment cycle. Treatment continues until the disease worsens.
The main goals of this part of the study are to evaluate the safety of CTIM-76 by monitoring dose-limiting toxicities (side effects severe enough to prevent further dose increases) during the first 28 days after treatment begins, and to assess the therapy’s antitumor activity by measuring the overall response rate (the proportion of patients whose tumors shrink according to standard criteria).
At the time of the analysis, 21 participants had received weekly CTIM-76 at doses ranging from 22.5 to 560 micrograms. Fourteen of those patients had platinum-resistant ovarian cancer. Among ovarian cancer patients, nine had received a median of seven prior lines of therapy. Nearly half (44%) had liver metastases, meaning the cancer had spread to the liver.
Of the seven ovarian cancer patients treated with active doses of CTIM-76 (140 to 280 micrograms) who had undergone at least one post-treatment tumor assessment by the time of the analysis, two achieved a confirmed partial response, meaning their tumors shrank by at least 30%, resulting in an overall response rate of 29%.
Overall, four patients (57%) achieved disease control, meaning their cancer either shrank or did not worsen during treatment. Three patients who achieved a confirmed partial response or stable disease saw that benefit maintained for at least six months.
CTIM-76 was generally well tolerated. Most side effects occurred during the first two treatment doses, were mild to moderate in severity, and resolved with standard medical care. Only one patient experienced a mild case of cytokine release syndrome, an immune-related reaction sometimes seen with therapies that activate T cells to attack cancer cells.
Pharmacokinetic data, which track how a therapy is absorbed, distributed, and cleared from the body, showed that CTIM-76 exposure generally increased with higher doses and supported testing the therapy on an every-three-week dosing schedule.
Findings from the next stage of development are expected to help determine the two doses and/or dosing schedules to be evaluated in the Phase 1b portion of the study in adults with platinum-resistant ovarian cancer, which is slated to begin in 2027.
“We are encouraged by the continued development of CTIM-76 as a potentially best-in-class CLDN6 T-cell engager that may offer a much-needed new therapeutic approach for patients with platinum-resistant ovarian cancer,” Lehr said.
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