ABL Bio's (298380) Dual Antibody Candidate, TovesiMig, Shows Promise in Cholangiocarcinoma Treatment
ABL Bio's dual antibody candidate, TovesiMig, has demonstrated positive results in a phase 2/3 clinical trial for second-line treatment of cholangiocarcinoma, a rare form of bile duct cancer. The study, named COMPANION-002, was conducted by the company's U.S. partner, Compass Therapeutics, and the findings were published in the Journal of Clinical Oncology (JCO) and presented at the European Society for Medical Oncology (ESMO).
The trial enrolled 168 patients with advanced cholangiocarcinoma who had previously received one line of systemic therapy. Patients were randomly assigned to either the TovesiMig plus paclitaxel combination arm (111 patients) or the paclitaxel monotherapy arm (57 patients).
The results showed that TovesiMig, when combined with paclitaxel, exhibited tumor response and delayed disease progression. However, the study did not meet the primary endpoint of statistically significant overall survival improvement. This raises questions about how the company will demonstrate survival benefits during the U.S. regulatory approval process.
Compass Therapeutics is now in further discussions with the U.S. Food and Drug Administration (FDA) to determine the next steps for TovesiMig's development and potential approval. Meanwhile, ABL Bio has announced that it will continue its own phase 1/2 clinical trial at the MD Anderson Cancer Center, focusing on the primary combination therapy for cholangiocarcinoma.
Despite the mixed results, investors remain optimistic about the potential of TovesiMig, as the treatment landscape for cholangiocarcinoma is limited, and the need for effective therapies is urgent. The market will closely monitor the ongoing discussions with the FDA and the progress of the MD Anderson trial.
Clinical Trial Results: Tobesimig and Paclitaxel Combination Therapy
The objective response rate was recorded at 18.0% for patients receiving the combination therapy with Tobesimig, compared to 5.3% for those treated with Paclitaxel alone. The median progression-free survival, a measure of the time until disease progression or death, was 4.7 months for the combination group and 2.6 months for the control group, showing a statistically significant improvement. However, the incidence of grade 3 or higher adverse events was higher in the combination group, with 93.5% reporting such events compared to 64.2% in the control group.
The interpretation of overall survival was impacted by crossover treatment. Among the 57 patients in the control group, 31 crossed over to receive the Tobesimig combination therapy upon disease progression. The company explained that this crossover significantly affected the comparison of survival outcomes between the two groups. Nevertheless, a post-hoc analysis adjusting for crossover treatment, included in this paper, did not demonstrate statistical significance. The overall survival hazard ratio was 0.85, with a 95% confidence interval of 0.59 to 1.26, and a p-value of 0.53.
Survival Advantage: A Key Focus for Compass's FDA Approval Process
The survival advantage is a critical factor in Compass's discussions with the U.S. Food and Drug Administration (FDA) regarding its approval process. In the FDA's feedback, released by Compass on September 22nd, the agency recommended conducting a trial to demonstrate survival benefits prior to the Biologics License Application (BLA) submission. Compass argues that given the urgent, unmet medical needs of cholangiocarcinoma patients and its previous clinical successes, an additional trial prior to the application is not necessary. The company has stated that it will continue preparing for the BLA submission while engaging with the FDA to determine the approval pathway.
Exploring Treatment Options
Compass is not only discussing the secondary treatment approval pathway but is also evaluating the potential for using Tovasemig as a first-line treatment for cholangiocarcinoma. The ongoing Phase 1/2 clinical trial, led by MD Anderson Cancer Center, combines Tovasemig with the standard first-line therapy of gemcitabine, cisplatin, and durvalumab. This trial differs from the COMPANION-002 trial, which combines paclitaxel with Tovasemig.
Primary Treatment Clinical Trial
The primary treatment clinical trial is planned to include approximately 50 patients. The initial cohort will be monitored for safety, and the treatment will be expanded to a larger group. The trial will assess the maximum tolerated dose of Tovasemig in combination and the progression-free survival rate at the six-month mark. Compass announced the first patient dosing in April of last year, prior to the FDA's feedback. In its business update in August, the company highlighted that the trial was ongoing and expected an increase in participating institutions. Currently, MD Anderson is recruiting patients for this study.
