Compass Therapeutics Eyes FDA Path After Tovecimig Trial Win

Key Points

• Compass Therapeutics says its lead drug tovecimig delivered positive results in the COMPANION-002 trial for advanced biliary tract cancer, meeting both its primary overall response rate endpoint and a key progression-free survival endpoint.
• The company plans an FDA meeting in early August to discuss the regulatory path for tovecimig, including potential BLA submission and whether approval could be full or accelerated, with a rolling filing possible later this year if aligned with regulators.
• Analysts and management said the trial’s overall survival readout was harder to interpret because of a high crossover rate, but Compass also highlighted encouraging subgroup data and safety that was consistent with expected VEGF-blockade effects such as hypertension.

Compass Therapeutics NASDAQ: CMPX Chief Executive Officer Tom Schuetz said the company is preparing for a key U.S. Food and Drug Administration meeting on tovecimig, its DLL4/VEGF bispecific antibody, after a randomized study in advanced biliary tract cancer met its primary endpoint and a key secondary endpoint.

Speaking during a Jefferies fireside chat moderated by biotech analyst Maury Raycroft, Schuetz said Compass is a Boston-based monoclonal antibody discovery and development company in oncology with four drugs in the clinic. The company’s most advanced program is tovecimig, which was evaluated in the COMPANION-002 study in patients with advanced biliary tract cancer who had received one prior line of therapy.

Tovecimig Study Met Response and PFS Endpoints

Schuetz said COMPANION-002 randomized 111 patients to tovecimig plus paclitaxel and 57 patients to paclitaxel alone. Patients in the control arm were allowed to cross over to the active arm after centrally confirmed progression, and 54% did so. Overall, 85% of patients in the study received tovecimig either at randomization or after crossover.

The study met its primary endpoint of overall response rate, with blinded independent central review used to assess responses. Schuetz said the paclitaxel arm had a 5.3% response rate, while the addition of tovecimig more than tripled the response rate and was statistically significant. He also cited a disease control rate of 61.3% in the combination arm versus 36.8% with paclitaxel alone, with a p-value of 0.0027.

Progression-free survival also improved significantly, Schuetz said, with a hazard ratio of 0.44 and a p-value of less than 0.0001. He described the result as a 56% reduction in the risk of progression associated with tovecimig.

“I would argue that this is a clinical endpoint because in this disease, where complications of biliary tract obstruction, any extension or prevention of progression in this study is very clinically meaningful,” Schuetz said.

Crossover Complicated Overall Survival Analysis

Schuetz said the intention-to-treat analysis did not show an overall survival difference, but he argued that the analysis was confounded by the high crossover rate. A prospective secondary endpoint called PFS2 evaluated patients who crossed over, comparing their progression-free survival on paclitaxel alone with their subsequent progression-free survival on tovecimig plus paclitaxel. In those patients, median PFS increased from 1.9 months on paclitaxel to 3.5 months after adding tovecimig, he said.

Schuetz also discussed a subset analysis of patients in the control arm. Patients who crossed over to receive tovecimig had median overall survival of 12.8 months, while those who received paclitaxel only had median overall survival of 6.1 months. Patients who received tovecimig at any point in the study had median overall survival of 9.9 months versus 6.1 months for paclitaxel alone, he said.

Raycroft asked about debate over the crossover subgroup, noting that crossover patients appeared to do better than patients initially randomized to active treatment. Schuetz said there was “no clear imbalance in prognostic factors” and said the finding was “definitely not post-study therapy.” He said one possible explanation was the small number of patients, while another was whether paclitaxel may prime the tumor microenvironment to make tovecimig more effective. Compass has begun preclinical work on that question, he said.

FDA Meeting Expected in August

Schuetz said Compass expects an FDA meeting in approximately the first half of August, with a full briefing package to be submitted around early July. He said meeting minutes could be available around Labor Day, after which the company would discuss the outcome publicly.

The goal of the meeting is to align with FDA on a pathway for submitting a Biologics License Application for tovecimig. If alignment is reached, Schuetz said Compass could begin a rolling BLA submission later this year and finish in the first quarter of next year. He said Fast Track designation could put a PDUFA date in the second half of next year and said he would be “shocked” if the company did not receive priority review in this indication.

Asked whether FDA could require a confirmatory study, Schuetz said both full approval and accelerated approval would be potential approval pathways. If a confirmatory trial is needed, he said one option could be a frontline study adding tovecimig to gemcitabine, cisplatin and durvalumab. Another possibility could be tovecimig plus paclitaxel versus investigator’s choice of chemotherapy, potentially in Europe to avoid crossover to commercial tovecimig plus paclitaxel, he said.

On safety, Schuetz said the most common adverse events tied to VEGF blockade were hypertension, while bone marrow suppression was related to paclitaxel. Asked about Grade 4 hypertension, he said there was “maybe one” event, though he was not certain, and said published algorithms for managing VEGF-blockade-associated hypertension were used in the study.

Other Pipeline Updates

Schuetz also highlighted CTX-8371, a PD-1/PD-L1 bispecific antibody. He said Compass presented dose-escalation Phase 1 data at ASCO, with no dose-limiting toxicities. In 15 treated patients, including six at the two highest dose levels, Schuetz said there were three responses, including in non-small cell lung cancer, Hodgkin’s lymphoma and triple-negative breast cancer, all after prior checkpoint inhibitor therapy.

Compass has moved CTX-8371 into cohort expansions in non-small cell lung cancer, triple-negative breast cancer and Hodgkin’s lymphoma. Schuetz said the expansion phase opened in the first quarter and was enrolling well, with more than 10 patients already enrolled. He said the company expects to present an update from the cohort expansions later this year.

Schuetz also discussed CTX-10726, Compass’ PD-1/VEGF-A bispecific antibody, which has entered Phase 1 testing. The company selected hepatocellular, renal, gastric and endometrial cancer indications based on settings where checkpoint inhibition and VEGF blockade are effective, he said. Schuetz said Compass may be able to present early data later this year, likely initial efficacy data rather than durability results.

Compass also plans to initiate a Phase 2 study later this year for its next-generation CD137 agonist in patients with NCAM-positive tumors, Schuetz said.

About Compass Therapeutics NASDAQ: CMPX

Compass Therapeutics, Inc is a clinical‐stage biotechnology company dedicated to the discovery and development of novel immuno‐oncology therapies. Headquartered in Cambridge, Massachusetts, the company focuses on engineering monoclonal antibody candidates designed to enhance T cell–mediated anti‐tumor responses. Compass leverages proprietary antibody platforms to identify and optimize biologics that modulate immune checkpoint pathways and the tumor microenvironment.

The company's lead programs include CTX-471, a bispecific antibody targeting both PD-1 and PD-L1 checkpoints, and DSP107, a CD47‐SIRPα pathway modulator aimed at disrupting “don't eat me” signals on cancer cells.

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