How was the phase 1\/2a FONTANA trial evaluating torvu-sam in PROC designed?Torvu-Sam in PROC: Updated FONTANA HighlightsConfirmed ORRs with torvu-sam were 61.7% in FR\u03b1-high, 57.1% in FR\u03b1-low, and 48.1% in FR\u03b1-ultralow\/null platinum-resistant ovarian cance.Median PFS with torvu-sam monotherapy was 9.7 months in FR\u03b1-high and 7.6 months in FR\u03b1-low disease.Three phase 3 TREVI-OC trials are set to evaluate the agent in ovarian cancer.<\/p>\n
The dose optimization part of the first-in-human, open-label study enrolled patients whose tumors expressed FR\u03b1 in at least 25% of tumor cells at or those with membrane intensity of 1+ or higher by immunohistochemistry. Enrollment criteria for both phases of parts trial required patients to be at least 18 years of age, have an ECOG performance status of 1 or less, histologically confirmed platinum-resistant ovarian cancer, measurable disease per RECIST 1.1 criteria, and at least 3 prior lines of therapy.<\/p>\n
The dose expansion portion of the trial enrolled patients with FR\u03b1-ultralow or -null tumors, defined as expression in fewer than 25% of tumor cells (n = 32).<\/p>\n
Patients were randomly assigned to receive intravenous torvu-sam at 2.4 mg\/kg, 2.0 mg\/kg, or 1.6 mg\/kg every 3 weeks. <\/p>\n
The primary end points were safety and tolerability, with secondary end points including ORR, DOR, PFS, and pharmacokinetics, and plasma circulating tumor DNA (ctDNA) assessment was an exploratory end point.<\/p>\n
Across the dose optimization portion and the additional dose expansion portion (n = 156), patients had a median age was 64 years (range, 26-82), 53.2% of patients had an ECOG performance status of 1, and the median number of prior lines of therapy was 2.0 (range, 1-4). <\/p>\n
Prior therapies included bevacizumab (Avastin) in 67.9% of patients, a PARP inhibitor in 60.3%, and mirvetuximab soravtansine-gynx (Elahere) in 2.6%. The median follow-up was 15.3 months (range, 1.0-24.2) in the dose optimization portion of the trial and 4.8 months (range, 0.4-15.2) in additional dose expansion part of the trial.<\/p>\n
What was the safety profile of torvutatug samrotecan across 3 doses in FONTANA?<\/p>\n
The safety analysis included patients treated in the Part A dose escalation, optimization and expansion parts of the trial at 1.6 mg\/kg of torvu-sam (n = 53), 2.0 mg\/kg (n = 90), and 2.4 mg\/kg (n = 64), with median exposure of 10.3 months, 5.6 months, and 8.1 months, respectively. <\/p>\n
All patients experienced at least 1 treatment-emergent adverse effect (TEAE) of any grade. Grade 3 or higher TEAEs occurred in 45.3%, 60.0%, and 82.8% of patients at the 1.6-mg\/kg, 2.0-mg\/kg, and 2.4-mg\/kg dose levels, respectively\/ Serious TEAEs occurred in 34.0%, 26.7%, and 53.1% of patients treated at each respective dose level. Additionally, TEAEs led to dose reductions in 13.2%, 18.9%, and 48.4% of patients and to discontinuation in 5.7%, 4.4%, and 14.1% at each dose level. One TEAE led to death at each of the 2.0-mg\/kg and 2.4-mg\/kg doses\/<\/p>\n
The most common TEAEs across dose levels included nausea, fatigue, neutropenia, anemia, and vomiting, with grade 3 or higher neutropenia and anemia more frequent at 2.4 mg\/kg.<\/p>\n
Did torvutatug samrotecan produce ctDNA molecular responses across FR\u03b1 subgroups?<\/p>\n
Among patients with detectable ctDNA at baseline who were evaluable at cycle 3 day 1 (n = 102), the complete molecular response rate (cMR was 47%, and the rate of any molecular response, was 87%. cMR and any-MR rates were 62% and 77%, respectively, in the FR\u03b1-ultralow\/null group (n = 13); 43% and 89% in the FR\u03b1-low group (n = 46); and 47% and 88% in the FR\u03b1-high group (n = 43).<\/p>\n
What phase 3 trials will evaluate torvutatug samrotecan in ovarian cancer?<\/p>\n
Data from FONTANA supported the design of 3 phase 3 trials. The phase 3 TREVI-OC-01 trial (NCT07218809) which is comparing torvu-sam vs mirvetuximab soravtansine in FR\u03b1-high platinum-resistant ovarian cancer and torvu-sam vs chemotherapy in FR\u03b1-low platinum-resistant ovarian cancer. The phase 3 TREVI-OC-02 trial (NCT07851025) is evaluating torvu-sam plus bevacizumab as first-line maintenance therapy in homologous recombination deficiency\u2013negative epithelial ovarian cancer, and finally the phase 3 TREVI-OC-03 trial (NCT07816666) which evaluating torvu-sam with or without bevacizumab as maintenance therapy in platinum-resistant ovarian cancer.<\/p>\n
ReferencesMeric-Bernstam F, Shapira Frommer R, Perets R, et al. Updated results from FONTANA: torvutatug samrotecan (torvu-sam), a folate receptor \u03b1 (FR\u03b1)-targeted antibody-drug conjugate (ADC), in patients (pts) with platinum-resistant ovarian cancer (PROC). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 1245RO.Long-Term and Novel ADC Data Dominate Top Gynecologic Cancer Abstracts at ESMO 2026. OncLive. Published October 14, 2026. Accessed October 24, 2026. https:\/\/www.onclive.com\/view\/long-term-and-novel-adc-data-dominate-top-gynecologic-cancer-abstracts-at-esmo-2026<\/a> <\/p>\n","protected":false},"excerpt":{"rendered":"How was the phase 1\/2a FONTANA trial evaluating torvu-sam in PROC designed?Torvu-Sam in PROC: Updated FONTANA HighlightsConfirmed ORRs…\n","protected":false},"author":2,"featured_media":641730,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[134,111,139,69],"class_list":["post-641729","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-new-zealand","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/641729","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=641729"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/641729\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/641730"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=641729"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=641729"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=641729"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}