Tovecimig

Biliary tract cancer is an adenocarcinoma of the biliary epithelium comprising intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, gallbladder cancer, and carcinoma of the ampulla of Vater, and accounts for less than 1% of cancers worldwide. For 2026 the American Cancer Society estimates 42,340 new cases of liver and intrahepatic bile duct cancer and 12,640 new cases of gallbladder and other biliary cancer in the United States, and Compass Therapeutics estimates approximately 26,500 people newly diagnosed with biliary tract cancer in the United States each year and over 200,000 worldwide. Age-adjusted cholangiocarcinoma incidence in the Surveillance, Epidemiology, and End Results program was 3.65 per 100 000 person-years from 2001 to 2017 and rose 43.8% over that period, driven by a 148.8% rise in intrahepatic disease against a 7.5% rise in extrahepatic disease. No registry reports the incidence of the second-line population directly. ABC-06 reported that 15% to 25% of participants receive second-line therapy, and in a United States commercial-claims cohort of 413 participants with advanced disease, 46% initiated a second line and 16.5% a third line; in a separate cohort, 514 of 1,298 participants (39.6%) died without receiving second-line therapy.

Survival is short and falls further after first-line progression. Five-year relative survival for liver and intrahepatic bile duct cancer is 21.9% overall, 13.4% for regional and 3.6% for distant disease, and median overall survival from diagnosis across 40,030 cholangiocarcinoma cases was 8 months. First-line chemoimmunotherapy extends survival modestly: median overall survival was 12.9 months with durvalumab plus gemcitabine and cisplatin versus 11.3 months with placebo plus chemotherapy in the TOPAZ-1 three-year update, and 12.7 versus 10.9 months in KEYNOTE-966. After progression, ABC-06 randomized 162 participants and reported median overall survival of 6.2 months with active symptom control plus FOLFOX versus 5.3 months with active symptom control alone (adjusted hazard ratio 0.69, 95% CI 0.50 to 0.97, p=0.031), 12-month survival of 25.9% and 11.4%, median progression-free survival of 4.0 months, and an objective response in 4 of 81 participants (5%). Grade 3 to 5 adverse events occurred in 56 of 81 participants (69%) receiving FOLFOX, including three chemotherapy-related deaths. Baseline tumour marker elevation stratifies the population sharply, with median overall survival falling from 8.9 months when none of CA19-9, CEA, and CA125 was elevated to 3.2 months when all three were.

No systemic regimen is approved by the FDA for second-line advanced biliary tract cancer. Guideline-recommended targeted options address FGFR2 fusions, IDH1 mutations, HER2 overexpression or amplification, BRAF V600E mutations, NTRK and RET fusions, and mismatch repair deficient or tumour mutational burden-high disease, but the COMPANION-002 investigators report frequencies of 4% to 5% for BRAF V600E, less than 1% for NTRK fusions, less than 1% for RET fusions, and 1% to 2% for microsatellite instability, and the sponsor states that approximately 85% of participants have no actionable mutation with an approved targeted therapy. Comprehensive genomic profiling of 91 biliary tract tumours at a single centre produced potentially actionable findings in 21 participants (23.1%) and genomically matched therapy in 7 (7.7%). The Pan-Asian adaptation of the ESMO guideline downgraded the second-line chemotherapy recommendation from level of evidence I to II and from grade A to B, citing the limited survival benefit and ABC-06 being the only positive phase 3 trial in the setting. Randomized evidence for liposomal irinotecan is inconsistent, with median blinded independent central review progression-free survival of 7.1 versus 1.4 months in NIFTY against 2.6 versus 2.3 months in NALIRICC, and 3.6 versus 1.8 months in a pooled analysis of 278 participants. The sponsor states that the regimens most commonly used in this setting are not labeled or approved for it, generally produce an objective response rate of about 5% or less, and are associated with a median overall survival of approximately six months.

Humanistic and economic burden are substantial. In ABC-06 there was no difference between arms in time to deterioration of the global health scale (adjusted hazard ratio 0.97, 95% CI 0.48 to 1.97, P = 0.937), and the EQ-5D utility value fell from 0.75 at baseline to 0.62 at month 4 in the active symptom control arm while declining less with FOLFOX. Long-term morbidity is dominated by recurrent biliary obstruction and infection: in a single-centre series of 171 participants receiving a palliative biliary stent, complications occurred in 91 (53%), cholangitis was the most frequent, and median survival was 75.5 days. In a United States claims cohort, 69.5% of participants had an all-cause inpatient hospitalization with a mean stay of 7 days per visit. Mean per-patient-per-month all-cause costs were $18,274 overall and rose with each line, from $19,589 in first line to $22,617 in second line and $33,534 in third line. Among working-age participants with cholangiocarcinoma, mean all-cause days absent per patient per month were 6.0 for intrahepatic and 4.3 for extrahepatic disease, and median indirect costs per patient per month from absenteeism, short-term disability, and long-term disability were $622, $635, and $690 for intrahepatic disease.

Tovecimig is an investigational bispecific antibody that binds delta-like ligand 4 and vascular endothelial growth factor A, given intravenously at 10 mg/kg on days 1 and 15 of each 28-day cycle with paclitaxel 80 mg/m2 on days 1, 8, and 15. A population pharmacokinetic model describes a two-compartment disposition with parallel linear and Michaelis-Menten elimination and a terminal half-life of approximately 5.7 days. The product is not approved in any jurisdiction. The FDA granted Fast Track designation in April 2024 for previously treated metastatic or locally advanced biliary tract cancer and orphan drug designation for biliary tract cancer in April 2026.

The registrational evidence is COMPANION-002, an open-label randomized phase 2/3 trial that enrolled 168 participants at 34 United States sites and allocated them 2:1 to tovecimig plus paclitaxel (111 participants) or paclitaxel alone (57 participants), with crossover permitted after centrally confirmed progression. Eligibility required radiologically documented progression after one prior gemcitabine and platinum containing regimen, an Eastern Cooperative Oncology Group performance status of 0 or 1, and ineligibility for an approved molecularly targeted therapy. The trial met its primary endpoint of objective response rate by blinded independent central review: 17.1% (19 of 111) including one complete response versus 5.3% (3 of 57), p=0.031, revised in the final analysis to 18.0% (20 of 111), p=0.0228. Median progression-free survival was 4.7 months versus 2.6 months (hazard ratio 0.44, p<0.0001).

The overall survival endpoint was not met. Median overall survival was 8.9 months with tovecimig plus paclitaxel versus 9.4 months in the control arm (hazard ratio 1.05, p=0.78), and a prespecified rank-preserving structural failure time adjustment gave 8.9 versus 9.4 months (hazard ratio 1.13, p=0.65). The sponsor attributes this to crossover: 31 of 57 control participants (54%) crossed over, so 142 of 168 participants (85%) received tovecimig and the control arm is not a tovecimig-naive comparator for survival. Three analyses favour tovecimig but are not randomized comparisons. In the 31 crossover participants, median progression-free survival was 3.5 months after crossover versus 1.9 months before it (hazard ratio 0.36, p=0.0016). Within the control arm, median overall survival was 12.8 months in crossover participants versus 6.1 months in non-crossover participants (hazard ratio 0.54, p=0.04), but the same participants had progressed faster on paclitaxel alone, with median progression-free survival of 1.9 versus 3.6 months (hazard ratio 2.31, p=0.007), indicating the two subgroups differed. Pooled median overall survival across all 142 participants who received tovecimig was 9.8 months.

Safety was reported for 108 and 53 participants. The most frequent treatment-emergent adverse events with tovecimig plus paclitaxel were hypertension (69%) and fatigue (67%), and the most common related grade 3 or higher events were hypertension (44%) and neutropenia (36%). Grade 3 or higher hypertension occurred in 52% of the tovecimig arm against 6% of the control arm. The sponsor reported no new safety signals.

Supporting evidence is early phase and smaller. In a Korean phase 1b/2 study, the objective response rate with tovecimig plus paclitaxel was 37.5% (9 of 24 participants, 95% CI 18.8 to 59.4), reaching 63.6% in the second-line subgroup and 15.4% in the third-line subgroup, with median duration of response and median progression-free survival both 9.4 months and 12-month overall survival of 53.0%; grade 3 or higher treatment-related adverse events occurred in 75% and neutropenia in 50.0%. The first-in-human phase 1 study dosed 45 participants with no dose-limiting toxicities, established recommended phase 2 doses of 10 and 12.5 mg/kg, and reported an objective response rate of 18.8% (3 of 16) at the recommended dose and hypertension in 37.8%. In COMPANION-003, a study of tovecimig monotherapy in third- and fourth-line metastatic colorectal cancer, the posted registry results record 2 responses among 49 participants, disease control in 28 of 49, median progression-free survival of 3.9 months, and median overall survival of 10.2 months.

Several limitations bear on interpretation. As of September 21, 2026 no COMPANION-002 publication or congress presentation existed, so all pivotal results come from sponsor documents filed with the U.S. Securities and Exchange Commission and are not peer reviewed; the complete dataset was selected for oral presentation at the October 2026 European Society for Medical Oncology Congress. The trial was powered to detect a 23% absolute difference in response rate with 90% power and a two-sided alpha of 0.05, so the observed difference of about 12 percentage points is smaller than the effect the sample size was planned around. Duration of response, participant disposition, deaths, serious adverse events, discontinuations due to adverse events, disease control rate, and the EORTC QLQ-C30 quality-of-life endpoint specified in the design publication have not been reported. All sites were in the United States, and eligibility excluded participants who could receive an approved molecularly targeted therapy, so the results apply to the population without an actionable alteration.

No price has been announced for tovecimig and no budget impact model, cost-effectiveness analysis, or health technology assessment of the product was identified, so its budgetary effect cannot be estimated from public evidence. Because the comparator in COMPANION-002 is generic paclitaxel given identically in both arms, the incremental cost of the regimen is essentially the price of tovecimig, additive to a low-cost chemotherapy backbone. Modelled United States costs for the displaced or accompanying therapies were an average sales price of $0.115 per milligram for paclitaxel with an intravenous administration cost of $140.16 for the first hour, and per-cycle costs of $26.76 for oxaliplatin, $52.48 for calcium folinate, and $18.57 for fluorouracil, against $11,730 per cycle for durvalumab and a reported average monthly United States price of $44,000 for futibatinib.

Population inputs are partly available but inconsistent between sources. Compass Therapeutics states that more than 26,500 people are diagnosed with biliary tract cancer in the United States each year, that more than 24,000 receive first-line treatment, that more than 17,000 receive second-line treatment, and that more than 15,000 are potentially eligible for tovecimig because approximately 85% have no actionable mutation; it places the addressable United States market in second-line biliary tract cancer at more than $3 billion. Market research reported approximately 19,000 incident United States cases in 2024 out of approximately 65,000 across the seven major markets. United States claims data give lower second-line rates than the company funnel: 46% of 413 participants with advanced biliary tract cancer initiated second-line therapy in one cohort, and 514 of 1,298 participants (39.6%) died without receiving second-line therapy in another. Real-world all-cause costs were $22,617 per patient per month during second-line therapy, of which more than 80% was disease-related, so a substantial cost base exists before any new agent is added.

Published economic analyses in this indication consistently found the price of the added biologic to be the dominant driver of the incremental cost-effectiveness ratio. Durvalumab added to gemcitabine and cisplatin was estimated at $381,864.39 per quality-adjusted life-year and pembrolizumab at $976,925 per quality-adjusted life-year from a United States payer perspective, both above the $150,000 per quality-adjusted life-year threshold applied. A 2026 systematic review of 20 economic studies in biliary tract cancer identified no cost-effectiveness analysis of second-line FOLFOX. The National Institute for Health and Care Excellence recommended zanidatamab in second-line biliary tract cancer in May 2026 with an acceptable incremental cost-effectiveness ratio at the upper end of £25,000 to £35,000 per quality-adjusted life-year and a confidential price. Tovecimig requires no companion diagnostic, so a budget impact model would not need the biomarker testing costs included in that submission. No analyst peak-sales forecast for tovecimig could be sourced from a document that states it.

Compass Therapeutics reported $180 million in cash at 30 June 2026 with a runway into 2028, and licensed the product from ABL Bio for $5 million upfront and a $6 million milestone, with up to $96 million in development and regulatory milestones and $303 million in commercial milestones plus tiered single-digit royalties in oncology; Handok holds South Korean rights and Elpiscience holds Chinese rights.

Second-line advanced biliary tract cancer is a setting with no FDA-approved systemic therapy for the approximately 85% of participants whose tumours carry no actionable alteration. The standard of care rests on a single positive phase 3 trial, ABC-06, in which FOLFOX extended median overall survival from 5.3 to 6.2 months and produced an objective response in 4 of 81 participants (5%), and the Pan-Asian adaptation of the ESMO guideline has downgraded that recommendation from level of evidence I to II and grade A to B.

Against that background, COMPANION-002 met its primary endpoint. Tovecimig plus paclitaxel roughly tripled the objective response rate relative to paclitaxel alone (18.0% versus 5.3%, p=0.0228, all responses confirmed by blinded independent central review) and nearly doubled median progression-free survival (4.7 versus 2.6 months, hazard ratio 0.44, p<0.0001). These are the largest randomized response and progression-free survival differences reported in this setting.

The trial did not demonstrate an overall survival benefit. Median overall survival was 8.9 months with tovecimig plus paclitaxel versus 9.4 months in the control arm (hazard ratio 1.05, p=0.78), and the prespecified crossover adjustment did not change that result (hazard ratio 1.13, p=0.65). Crossover of 31 of 57 control participants (54%) means 142 of 168 participants (85%) received tovecimig, which limits what the survival comparison can show, but the analyses the sponsor offers in support of a survival effect are post hoc comparisons of non-randomized subgroups, and one of them shows the crossover and non-crossover subgroups differed in progression rate on paclitaxel alone before crossover occurred.

For a pharmacy and therapeutics committee, four considerations follow. First, the efficacy claim rests on response rate and progression-free survival, not survival, in a population whose median survival is under one year. Second, all pivotal results are sponsor documents filed with the U.S. Securities and Exchange Commission and are not peer reviewed; duration of response, disposition, deaths, serious adverse events, discontinuations, disease control rate, and the prespecified quality-of-life endpoint are unreported, and the complete dataset was scheduled for presentation in October 2026. Third, the added toxicity is measurable and manageable but not trivial, with grade 3 or higher hypertension in 52% of the tovecimig arm against 6% of the control arm. Fourth, no price has been announced, no economic model exists, and because the comparator is generic paclitaxel the whole incremental cost of the regimen will be the price of tovecimig; the sponsor guides to a Biologics License Application in the fourth quarter of 2026 and potential approval and launch in 2027, so a placement decision is likely to be required before peer-reviewed evidence is available.