COMPANION-003

24 evidence topics · 4 sources

Objective

Registered objective

“This study is designed as an open-label, adaptive Simon Two-Stage study to evaluate the efficacy of CTX-009 in patients with metastatic colorectal cancer.” (opens the source at this quote in a new tab)

Location and study date

Study dates and status: registry record

Milestone	Registry record
Study start (actual)	“2022-12-08”
Primary completion (actual)	“2025-05-15”
Study completion (actual)	“2025-05-15”
Enrollment (actual)	“49”
Results first posted	“2026-07-28”

Region of enrollment

“United States 49” (opens the source at this quote in a new tab)

Presentation of the results

“Tovecimig’s Phase 2 monotherapy data in patients with advanced, metastatic CRC treated in the third- and fourth-line settings will be presented at the 2026 ASCO GI Cancers Symposium in San Francisco on Saturday, January 9, 2026.” (opens the source at this quote in a new tab)

Study design

Registered design details

Design feature	Registry record
Primary purpose	“Treatment”
Allocation	“N/A”
Interventional model	“Single Group Assignment”
Masking	“None (Open Label)”

Two-stage enrollment plan

“A Simon Two-Stage adaptive design will enroll approximately 37 patients into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled.” (opens the source at this quote in a new tab)

Eligibility criteria

Line of therapy

“A Phase 2 Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer Who Have Received Two or Three Prior Systemic Chemotherapy Regimens” (opens the source at this quote in a new tab)

Prior bevacizumab exposure of the enrolled population

“Tovecimig demonstrated monotherapy activity, with an overall response rate of 5% (2 out of 40 patients), in heavily pre-treated patients, all of whom had previously been treated with bevacizumab (~51% had been treated with two or more prior rounds of bevacizumab).” (opens the source at this quote in a new tab)

Treatment

Dose and schedule

“10 mg/kg body weight by IV infusion over 1 hour every 2 weeks” (opens the source at this quote in a new tab)

“IV infusion administered on day 1 and 15 of every 28-day cycle” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using overall response rate as the primary endpoint

Registered primary outcome measure

Outcome measure	Measure description	Time frame
“Overall Response Rate”	“Percentage of patients whose best overall response is assessed as complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions.”	“From first dose of CTX-009 until treatment discontinuation (an average of 16 weeks)”

Response-rate benchmark used to interpret the endpoint

“Tovecimig’s activity in this patient population differentiates it from other anti-VEGF agents, which have shown 1.0-1.5% response rates in this patient population.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Planned and actual enrollment and the stage 1 stopping decision

“The protocol required enrolment of approximately 40 (minimum of 37) response evaluable participants. A total of 49 participants were enrolled in Stage 1, yielding 40 response evaluable participants. The study results did not meet the protocol-defined criterion for progression to Stage 2, and thus enrollment ended after Stage 1.” (opens the source at this quote in a new tab)

Description of analysis sets

Population analyzed for the posted outcome measures

“Overall Number of Baseline Participants 49” (opens the source at this quote in a new tab)

Population analyzed for duration of response

“Calculated for patients who had confirmed complete or partial response” (opens the source at this quote in a new tab)

Results

Participant disposition

Reasons for not completing the study

Disposition	Participants
Started	“49”
Completed	“0”
Not completed	“49”
Death	“34”
Lost to follow-up	“1”
Withdrawal by subject	“7”
Study termination by sponsor	“7”

Baseline characteristics

Age and region

Characteristic	CTX-009 10 mg/kg (n=49)
Mean age, years (standard deviation)	“58.6(11.54)”
Region of enrollment	“United States 49”

Efficacy results

Response and survival as reported by the sponsor in the response-evaluable population

“Tovecimig demonstrated monotherapy activity, with an overall response rate of 5% (2 out of 40 patients), in heavily pre-treated patients, all of whom had previously been treated with bevacizumab (~51% had been treated with two or more prior rounds of bevacizumab). Tovecimig also demonstrated a DCR of 68% (27 out of 40), median PFS of 3.9 months and median OS of 10.2 months.” (opens the source at this quote in a new tab)

Posted time-to-event outcomes in all treated participants

Outcome measure	Median	Interquartile range	Participants analyzed
Duration of response, weeks	“14.4”	“(13.3 to 15.4)”	“2”
Progression-free survival, months	“3.9”	“(1.8 to 5.8)”	“49”
Overall survival, months	“10.2”	“(5.3 to 17.8)”	“49”

Association between DLL4 expression and outcome

“Although DLL4 expression on colorectal tumors is a negative prognostic factor, the data indicate that patients with DLL4-positive tumors did better with tovecimig therapy than patients with DLL4-negative tumors.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Overall adverse event rates

Category	Affected / at risk (%)
All-cause mortality	“34/49 (69.39%)”
Serious adverse events	“14/49 (28.57%)”
Other, non-serious adverse events	“47/49 (95.92%)”

Most frequent non-serious adverse events

Adverse event	Affected / at risk (%)
Hypertension	“22/49 (44.90%)”
Proteinuria	“18/49 (36.73%)”
Nausea	“14/49 (28.57%)”
Fatigue	“13/49 (26.53%)”
Weight decreased	“11/49 (22.45%)”
Headache	“10/49 (20.41%)”
Cardiac failure	“9/49 (18.37%)”
Diarrhoea	“8/49 (16.33%)”
Decreased appetite	“8/49 (16.33%)”

Nature of the reported cardiac failure events

“due to asymptomatic B-type natriuretic peptide (BNP) elevation, Grade 1” (opens the source at this quote in a new tab)

Sponsor characterization of the safety profile

“Tovecimig’s safety profile was generally consistent with prior studies with hypertension as the most common treatment-emergent adverse event, all of which occurred in patients with a prior history of hypertension.” (opens the source at this quote in a new tab)

Study limitations

Summary

COMPANION-003 studied tovecimig as monotherapy in metastatic colorectal cancer, not in biliary tract cancer, so it informs the safety profile and the DLL4 biomarker hypothesis rather than the indication. It was open-label and single-arm, enrolled 49 participants at sites in the United States only, and stopped after stage 1 because the protocol-defined criterion for progression to stage 2 was not met. Only 2 of 40 response-evaluable participants responded, and duration of response was estimated from those 2 participants, so the 14.4 week median is not a stable estimate. The sponsor reports response and disease control against a denominator of 40 response-evaluable participants while the registry posts outcomes against all 49 enrolled, so the two sets of figures are not interchangeable. The registry record specifies RECIST version 1.0 for the response definitions although the drug program otherwise uses RECIST version 1.1. No participant completed the study, 34 of 49 participants died, 7 withdrew, and 7 ended participation when the sponsor terminated the study, so follow-up was truncated. The comparison with anti-VEGF agents showing 1.0% to 1.5% response rates is a cross-trial comparison, and the statement that participants with DLL4-positive tumors did better is an unadjusted subgroup observation. Quality-of-life outcomes were not collected, and the results are available from the registry and sponsor filings rather than a peer-reviewed publication.