Summary: expected outcomes and the benchmarks they are measured against

COMPANION-002 defines the outcomes tovecimig plus paclitaxel is expected to achieve. The primary endpoint is the proportion of participants whose best overall response is complete or partial response by RECIST version 1.1, and the secondary endpoints are progression-free survival, duration of response, overall survival, disease control rate, and treatment-emergent adverse events.

On the primary endpoint, the final analysis reported an objective response rate of 18.0% (20 of 111 participants) with tovecimig plus paclitaxel versus 5.3% with paclitaxel alone (p=0.0228), revised from the 17.1% versus 5.3% (p=0.031) reported at the April 2025 top-line analysis after one participant was adjudicated by blinded independent central review as a partial response. Progressive disease as best overall response occurred in 16.2% of the combination arm versus 42.1% of the control arm. On the key secondary endpoint, median progression-free survival by blinded independent central review was 4.7 months versus 2.6 months (hazard ratio 0.44, p<0.0001). Overall survival did not reach statistical significance: median overall survival was 8.9 months with the combination and 9.4 months in the control arm (hazard ratio 1.05, p=0.78), which the sponsor attributes to 31 of 57 control participants (54%) crossing over, with the result that 142 of 168 participants (85%) received tovecimig and the pooled median overall survival across the study was 8.9 months.

These values are to be read against the benchmarks the sponsor and the guideline evidence describe for second-line treatment: an objective response rate of approximately 5% or less and a median overall survival of approximately six months with the regimens most commonly used off-label; a median overall survival of 6·2 months with FOLFOX versus 5·3 months with active symptom control and an objective response in 4 of 81 participants (5%) in ABC-06; and a median blinded independent central review progression-free survival of 7·1 months with liposomal irinotecan plus fluorouracil and leucovorin in NIFTY against 2·6 months in NALIRICC. Duration of response has not been reported, and no health-related quality of life outcome for tovecimig has been reported in the cited sources. The complete dataset was scheduled for oral presentation at the October 2026 ESMO Congress.

Endpoints COMPANION-002 is designed to measure

Field	Registry record
Primary outcome measure	“Best Overall Response”
Primary outcome description	“Percentage of patients whose Best Overall Response (BOR) is assessed as Complete Response (CR) or Partial Response (PR) as assessed by RECIST 1.1”
Secondary outcome measure	“Progression Free Survival”
Secondary outcome measure	“Duration of Response”
Secondary outcome measure	“Overall Survival”
Secondary outcome measure	“Disease Control Rate”

Response rate achieved in the final analysis

“In the final data analysis, the overall response rate (ORR), the primary endpoint in the study, improved to 18.0% (20/111 patients) in the tovecimig combination arm from a previously reported 17.1%.” (opens the source at this quote in a new tab)
“With this change, the p-value improved to 0.0228 compared to paclitaxel alone (ORR of 5.3% in the paclitaxel arm).” (opens the source at this quote in a new tab)

“The study also showed differences between treatment arms for other efficacy measures, including progressive disease (PD) rates of 16.2% in patients on tovecimig in combination with paclitaxel versus 42.1% in patients on paclitaxel alone.” (opens the source at this quote in a new tab)

Progression-free survival and overall survival achieved

“Tovecimig in combination with paclitaxel demonstrated a statistically significant improvement in median PFS of 4.7 months compared to 2.6 months for paclitaxel alone (HR=0.44, p<0.0001). Progression was confirmed in each case by BICR.” (opens the source at this quote in a new tab)
“In the ITT OS analysis, tovecimig in combination with paclitaxel had a median OS of 8.9 months compared to 9.4 months for the control arm, which included 26 patients (46%) who received paclitaxel alone and 31 patients (54%) who crossed over to receive tovecimig in combination with paclitaxel (HR=1.05, p=0.78).” (opens the source at this quote in a new tab)
“Including crossover, 85% of patients in the study received tovecimig in combination with paclitaxel and the pooled median OS for all patients in the study was 8.9 months, which is also substantially longer than chemotherapy benchmarks of approximately 6 months.” (opens the source at this quote in a new tab)

Comparator benchmarks for response and survival in the second-line setting

“The combinations of therapeutics used in this setting, which are not labeled for this indication, generally have an ORR of ~5% or less and patients face a median overall survival of approximately six months.” (opens the source at this quote in a new tab)

“Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4–7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1–5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50–0·97]; p=0·031).” (opens the source at this quote in a new tab)
“Objective response was observed in four (5%) of 81 patients in the ASC plus FOLFOX group: one (1%) patient had a complete response and three (4%) patients had a partial response.” (opens the source at this quote in a new tab)

“second-line FOLFOX resulted in a median progression-free survival of 4·0 months (95% CI 3·2–5·0), a median overall survival of 6·2 months (95% CI 5·4–7·6), and an objective response rate of 5%.” (opens the source at this quote in a new tab)

Quality of life during second-line liposomal irinotecan

“Our quality of life analysis showed that the addition of liposomal irinotecan did not impair global health status.” (opens the source at this quote in a new tab)

Tovecimig (CTX-009)

Expected outcomes of therapy