On May 31, 2026 Eli Lilly and Company (NYSE: LLY) reported results from the Phase 3 LIBRETTO-432 clinical trial of Retevmo (selpercatinib) as adjuvant therapy versus placebo in patients with early-stage (IB-IIIA) rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in investigator-assessed event-free survival (EFS) with selpercatinib reducing the risk of disease recurrence or death by 83% versus placebo in the primary analysis population.

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These data will be simultaneously published in the New England Journal of Medicine and presented during the Plenary Session at the 2026 ASCO (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, Illinois, as well as featured in the meeting’s press program.

"Patients with early-stage RET fusion-positive lung cancer face high recurrence risk, yet unlike those with EGFR or ALK alterations, have lacked a proven targeted treatment option," said Jonathan Goldman, M.D., Professor of Medicine and Director of Clinical Trials at University of California, Los Angeles. "These LIBRETTO-432 results provide strong evidence that treating with selpercatinib after surgery or radiation can significantly lower that risk. The magnitude of benefit seen from adjuvant treatment with selpercatinib reinforces that comprehensive genomic testing at diagnosis is essential for all people with lung cancer and could lead to changes in clinical practice for treating early-stage RET-positive disease."

LIBRETTO-432 is the first and only randomized Phase 3 study to evaluate the safety and efficacy of a selective RET kinase inhibitor as adjuvant therapy in this population. The trial enrolled 151 patients who were randomized 1:1 to receive selpercatinib 160mg twice daily or placebo for up to three years following completion of definitive radiotherapy or surgery with curative intent with or without adjuvant chemotherapy.

At a median follow-up of 24 months, investigator-assessed EFS in the primary analysis population (patients with stage II-IIIA disease, n=109) was significantly improved with selpercatinib compared to placebo (HR: 0.17 [95% CI, 0.06 to 0.51]; p<0.001). The EFS rate at 24 months was 92% [95% CI, 75.4 to 97.2] for selpercatinib compared to 61% [95% CI, 44.2 to 74.3] for placebo. The median EFS was not reached for selpercatinib versus 31.8 months for placebo. In the overall study population (patients with stage IB-IIIA disease, n=151), EFS was consistent, also favoring selpercatinib (HR: 0.17 [95% CI, 0.06 to 0.49]; p<0.001). The EFS rate at 24 months was 94% [95% CI, 81.5 to 98.0] in the selpercatinib group and 70% [95% CI, 55.5 to 80.1] in the placebo group. Results were consistent across blinded independent central review and key subgroups in both the primary analysis set and in the overall study population. Overall survival results trended in favor of selpercatinib, but were immature at the time of this analysis with few events observed.

The overall safety profile of selpercatinib in LIBRETTO-432 was generally consistent with previously reported trials in the selpercatinib development program. The most common Grade 3 or higher adverse events (AEs) were increased alanine aminotransferase (ALT) (17% in the selpercatinib group versus 1% in the placebo group) and increased aspartate aminotransferase (AST) (19% in the selpercatinib group versus 3% in the placebo group), but were manageable with dose-modification.

"Selpercatinib has changed the treatment paradigm for patients with advanced RET-positive lung cancer, and now the substantial reduction in the risk of recurrence or death seen in LIBRETTO-432 highlights the potential for it to also become a new standard of care in the adjuvant setting for patients with early-stage RET-positive NSCLC," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "These compelling results highlight the importance of bringing our effective medicines to patients early in their disease course when their impact can be greatest, and bring further urgency to the need for comprehensive biomarker testing for all lung cancers at diagnosis to enable effective therapy against EGFR, ALK and RET and for the development of medicines targeting emerging new biomarkers."

Lilly plans to submit results from LIBRETTO-432 to global health authorities. For more information on the LIBRETTO Phase 3 clinical trial program, please visit clinicaltrials.gov.

About LIBRETTO-432
LIBRETTO-432 is a Phase 3, global, multicenter, randomized, double-blind, controlled clinical trial of selpercatinib versus placebo in patients with RET fusion-positive NSCLC following completion of definitive radiotherapy or surgery with curative intent, and other adjuvant therapy, if indicated. The trial enrolled 151 patients who were randomized 1:1 to receive either selpercatinib or placebo as adjuvant therapy for RET fusion-positive NSCLC. The primary endpoint is EFS as assessed by investigator in the primary analysis population, which was comprised of patients with stage II-IIIA RET fusion-positive NSCLC. Secondary endpoints include EFS as assessed by investigator in the overall population, overall survival (OS), EFS as assessed by blinded independent central review (BICR), time to distant disease recurrence in the central nervous system (CNS) as assessed by investigator and BICR, progression-free survival on the next line of treatment (PFS2), positive predictive value (PPV) of RET tests from investigator-identified laboratories with respect to the Lilly-designated RET test, safety and tolerability.

About Retevmo
Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity.1

INDICATIONS FOR RETEVMO (selpercatinib)

RETEVMO is a kinase inhibitor indicated for the treatment of:

Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test
IMPORTANT SAFETY INFORMATION FOR RETEVMO (selpercatinib)

Hepatotoxicity: Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on severity.

Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD.

Hypertension occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on severity.

Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity.

Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage.

Retevmo can cause hypersensitivity, including severe skin reactions such as Stevens-Johnson Syndrome. All grade hypersensitivity occurred in 6% of patients receiving Retevmo, including Grade 3 in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. Stevens-Johnson Syndrome has been observed in the post-marketing setting. Discontinue Retevmo in patients with Stevens-Johnson Syndrome. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity.

Tumor lysis syndrome (TLS) occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established.

Retevmo can cause hypothyroidism. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity.

Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose.

Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%).

Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%).

Serious adverse reactions occurred in 44% of patients who received Retevmo in LIBRETTO-001. The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001; fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1).

Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431. The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431; fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each).

Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%).

Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%).

Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001, were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%).

Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%).

Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally acting antacid).

Concomitant use of strong and moderate CYP3A inhibitors increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently.

Concomitant use of strong and moderate CYP3A inducers decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers.

Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.

Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with P-gp or BCRP substrates increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling.

No dosage modification is recommended for patients with mild to severe renal impairment (estimated Glomerular Filtration Rate [eGFR] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease [MDRD] equation). A recommended dosage has not been established for patients with end-stage renal disease.

Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment.

Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets.

(Press release, Eli Lilly, MAY 31, 2026, View Source [SID1234666244])

On May 30, 2026 ImPact Biotech, a clinical-stage biotechnology company focused on developing Padeliporfin Vascular Targeted Photodynamic therapy (VTP) to treat a range of solid tumors, reported updated data from the ongoing Phase 1 trial of Padeliporfin VTP treatment in patients with unresectable locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) and from ENLIGHTED, the Company’s ongoing Phase 3 study in patients with low-grade upper tract urothelial carcinoma (UTUC). These data will be shared during two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 29-June 2, 2026, in Chicago, IL.

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"Today’s presentations underscore the continued clinical progress across both our expanding development efforts in LA-PDAC and our pivotal Phase 3 ENLIGHTED study in LG-UTUC," said Eyal Morag, M.D., Chief Medical Officer of ImPact Biotech. "The updated early Phase 1 results in LA-PDAC, including successful resection outcomes observed to date, are encouraging and support initial validation of our VTP platform and its potential broader application in difficult-to-treat solid tumors. Given the substantial unmet need and large addressable patient population in LA-PDAC, we believe Padeliporfin VTP may offer a differentiated therapeutic option with the potential to convert these patients to surgically resectable candidates."

"In parallel, updated data from the ENLIGHTED trial continue to demonstrate compelling complete response rates, encouraging durability, and a favorable tolerability profile, reinforcing Padeliporfin VTP’s potential to offer a clinically meaningful, organ-sparing treatment option for patients with low-grade UTUC," continued Dr. Morag. "We look forward to pursuing strategic opportunities for the potential commercialization of Padeliporfin VTP in LG-UTUC, while advancing clinical development in both indications."

Key updated results from the Phase 1 study of Padeliporfin VTP in LA-PDAC:

The Phase 1 LA-PDAC trial is a three part dose-escalation and expansion study evaluating Padeliporfin VTP in patients with vascular encasement deeming them ineligible for surgical resection. As of April 24, 2026, the data cut-off for the poster presentation at ASCO (Free ASCO Whitepaper), seven patients had completed treatment across the 200 mW/cm and the 400 mW/cm dose levels without clinically significant dose-limiting toxicities (DLTs) and were evaluable for potential surgery.

Efficacy Profile:

5 of the 7 (71%) patients underwent successful surgery following Padeliporfin VTP treatment, including 4 of the 7 patients (57%) with R0 margins.

Safety and Tolerability Profile:

Padeliporfin VTP was well-tolerated with no complications observed related to arterial injury, thrombosis, ischemia, or significant VTP-related morbidity.

Early clinical observations of Padeliporfin in LA-PDAC support advancement of the program, showing potential to convert patients with unresectable stage III LA tumors to surgically resectable candidates. Subject to future discussions with the U.S. Food and Drug Administration (FDA), the Company believes this program may have potential to move directly into a registrational study.

Key updated results from the Phase 3 ENLIGHTED study of Padeliporfin VTP:

The Phase 3 ENLIGHTED study is a single arm, non-randomized, open-label, pivotal trial evaluating Padeliporfin VTP for the treatment of low-grade UTUC. As of April 20, 2026, the data cut-off for the poster presentation at ASCO (Free ASCO Whitepaper), Padeliporfin VTP demonstrated a consistent efficacy profile with 50 of the 72 (70%) response-evaluable patients achieving a CR at the end of Primary Response Evaluation (PRE). 18 of the 21 (85.7%) response-evaluable patients who completed the Maintenance Treatment Phase (MTP) sustained CRs in the treated area for at least 12 months as of the data cutoff date, reaching a current median duration of response in the treated area of 23.9 months based on available follow-up. Padeliporfin VTP treatment was well-tolerated and has demonstrated a consistent and acceptable safety profile to date.

ImPact has completed enrollment in ENLIGHTED with topline data expected in 2026. Following positive ongoing discussions with the FDA, including a recent Type C meeting which confirmed the proposed registrational pathway and streamlined package requirements allowing ImPact to leverage supplemental non-clinical modules from a prior NDA submission for Padeliporfin VTP in advanced localized prostate cancer, the Company is on track to submit an NDA in low-grade UTUC in 2027. ImPact is pursuing strategic partnering opportunities to support the commercialization of this program.

ASCO Presentation Details:

Poster Title: Phase I Light-Dose Escalation Study in Locally Advanced Pancreatic Ductal Adenocarcinoma: Intra-Arterial (IA) Padeliporfin Vascular-Targeted Photodynamic Therapy (VTP)
Presenter: Nadine Abi-Jaoudeh, M.D., Professor of Clinical Radiology, University of California Irvine
Poster Number: 236a
Session Title: Gastrointestinal Cancer: Gastroesophageal, Pancreatic, and Hepatobiliary
Session Date & Time: Saturday, May 30, 2026 at 9:00 AM CT

Poster Title: Advancing Treatment of Low-Grade Upper Tract Urothelial Carcinoma (LG UTUC) with Padeliporfin Vascular-Targeted Photodynamic Therapy (VTP): The ENLIGHTED Phase 3 Trial
Presenter: Vitaly Margulis, M.D., Professor of Urologic Oncology, University of Texas Southwestern Medical Center
Poster Number: 115a
Session Title: Genitourinary Cancer: Kidney and Bladder

Session Date & Time: Sunday, May 31, 2026 at 9:00 AM CT

(Press release, ImPact Biotech, MAY 30, 2026, View Source [SID1234666289])

On May 30, 2026 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported encouraging Health-Related Quality of Life (HRQoL) data from its Phase 3 COMPETE trial in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The data showed favorable and durable quality of life outcomes for patients receiving non-carrier-added (n.c.a.) ¹⁷⁷Lu-edotreotide (also known as ITM-11 or ¹⁷⁷Lu-edotreotide) compared to everolimus, a systemic standard of care treatment.

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The data were presented by Jaume Capdevila, MD, PhD, study investigator and senior medical oncologist at Vall d’Hebron University Hospital, Barcelona, Spain in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held from May 29 – June 2, 2026 in Chicago, Illinois.

"For patients with GEP-NETs, treatment decisions are not only about preventing disease progression, but also about preserving daily functioning and quality of life," said Jaume Capdevila, MD, PhD, study investigator and senior medical oncologist at Vall d’Hebron University Hospital, Barcelona, Spain. "The COMPETE data suggest more favorable patient-reported outcomes with ¹⁷⁷Lu-edotreotide compared with everolimus, including a longer median time to deterioration in quality of life. Together with the previously reported efficacy results, these findings add important patient-centered evidence to inform treatment discussions."

The quality of life analyses included 309 patients (¹⁷⁷Lu-edotreotide, n=207; everolimus, n=102). More than 85% of patients completed the two validated EORTC QLQ questionnaires1 throughout the study: the 30-item QLQ-C30 and the 21-item QLQ-GI.NET21. Both surveys use standardized 0-100 scales to assess overall health, physical and social functioning, and GEP-NET symptom burden. Patients completed questionnaires at baseline, monthly in year one, and every three months thereafter.

Key QoL Findings:

On average, patients on the ¹⁷⁷Lu-edotreotide arm maintained their quality of life (score change: +0.9) while patients in the everolimus arm experienced a meaningful decline in quality of life (score change: -9.9)
Patients on ¹⁷⁷Lu-edotreotide experienced a longer period of time before their quality of life began to decline: a median of 10.3 months vs. 2.3 months for everolimus
A meaningful overall improvement in quality of life was reported by 43.5% of patients on ¹⁷⁷Lu-edotreotide vs. 30.4% of those on everolimus
Among those who improved, median duration of improvement was 22.0 months vs. 10.2 months, respectively
"These additional COMPETE results provide important insights into quality of life during treatment with ¹⁷⁷Lu-edotreotide, and further add to the clinical data generated to date," said Dr. Celine Wilke, chief medical officer of ITM. "Balancing treatment benefit, risk and personal preference to improve overall patient health remains a top priority for ITM, alongside delivering meaningful clinical outcomes through targeted radiopharmaceuticals."

¹⁷⁷Lu-edotreotide is an investigational product pending review by the U.S. Food and Drug Administration (FDA) and is not approved by any regulatory authority for the safety and/or efficacy of any intended use.

About the COMPETE Trial
The COMPETE trial (NCT03049189) evaluated ¹⁷⁷Lu-edotreotide (ITM-11), a proprietary, synthetic, targeted radiotherapeutic investigational agent compared to everolimus, a targeted molecular therapy, in patients with inoperable, progressive Grade 1 or Grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This trial met its primary endpoint, with ¹⁷⁷Lu-edotreotide demonstrating clinically and statistically significant improvement in progression-free survival (PFS) compared to everolimus. ¹⁷⁷Lu-edotreotide is also being evaluated in COMPOSE, a Phase 3 study in patients with well-differentiated, aggressive Grade 2 or Grade 3, somatostatin receptor (SSTR)-positive GEP-NETs.

(Press release, ITM Isotopen Technologien Munchen, MAY 30, 2026, View Source [SID1234666288])

On May 30, 2026 Pfizer Inc. (NYSE: PFE) reported detailed results from the pivotal Phase 3 TALAPRO-3 study of TALZENNA (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI (enzalutamide), an androgen receptor pathway inhibitor (ARPI), in men with homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC). These results will be presented today in a late-breaking oral presentation (Abstract LBA5007) at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in The New England Journal of Medicine.

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TALZENNA plus XTANDI demonstrated a 52% reduction in the risk of radiographic progression or death compared to placebo plus XTANDI (Hazard Ratio [HR] of 0.48; 95% Confidence Interval [CI], 0.36–0.65; p ˂ 0.0001). At three years, radiographic progression-free survival (rPFS) rates were estimated at 77% in patients treated with TALZENNA plus XTANDI versus 56% in patients treated with placebo plus XTANDI. With a median follow-up of over 37 months, median rPFS was not reached in the TALZENNA plus XTANDI arm and was 46 months with placebo and XTANDI.

The rPFS benefit observed with TALZENNA plus XTANDI was consistent across pre-specified groups with various patient and disease characteristics, including age, Gleason score, geographic region, prostate-specific antigen (PSA) level, and BRCA vs. non-BRCA HRR gene alteration status. At three years, rPFS rates were estimated at 77% vs. 49% in patients with cancer harboring BRCA alterations (HR, 0.37; 95% CI, 0.22–0.61) and 76% vs. 60% in patients with cancer with non-BRCA alterations (HR, 0.57; 95% CI, 0.39–0.82), compared with placebo plus XTANDI.

"Delaying progression to castration‑resistant disease, the most symptomatic and lethal phase of prostate cancer, remains a significant challenge to patients with mCSPC – especially to those with HRR gene alterations, who often experience poorer outcomes," said Neeraj Agarwal, M.D., FASCO, Presidential Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah and global lead investigator for TALAPRO-3. "With more than three years of follow‑up and median radiographic progression‑free survival not reached, TALZENNA plus XTANDI demonstrated durable disease control across a broad HRR‑altered population, including patients with BRCA and non‑BRCA alterations. These findings underscore the importance of genetic testing as part of routine care and highlight the potential for TALZENNA plus XTANDI to meaningfully improve the outcomes of patients with HRRm mCSPC."

Interim overall survival (OS) results showed a strong trend toward improved OS, a key secondary endpoint, with median OS not reached in either treatment arm (HR, 0.77; 95% CI, 0.56–1.04; p = 0.09). TALZENNA plus XTANDI also improved time to PSA progression (HR, 0.51; 95% CI, 0.37–0.71; p < 0.0001) and time to subsequent anti-cancer therapy (HR, 0.51; 95% CI, 0.38–0.70; p < 0.0001) vs. placebo plus XTANDI. The trial remains ongoing, and OS will be formally assessed at the final analysis.

In TALAPRO-3, the safety profile of TALZENNA plus XTANDI was consistent with the known profiles of each agent, and no new safety signals were identified. The most common treatment-emergent adverse events (TEAEs) in the TALZENNA plus XTANDI group were anemia, fatigue, decreased neutrophil count, and asthenia. The most common grade 3 or higher TEAE was anemia, reported by 51% in the TALZENNA plus XTANDI group and 3% in the control group. Five percent of patients discontinued TALZENNA due to anemia. TEAEs were generally manageable with dose modifications and supportive care as needed.

"Men with HRR gene-mutated metastatic prostate cancer face significant challenges, with faster disease progression and limited treatment options, making it critical to intervene as early in the course of disease as possible," said Jeff Legos, Chief Oncology Officer, Pfizer. "The benefit seen with TALZENNA plus XTANDI across a full spectrum of HRR gene alterations reinforces its potential to fundamentally change clinical practice, giving patients significantly more time before disease progression as compared to the current standard of care."

Prostate cancer is the second most common cancer in men worldwide, with an estimated 1.5 million new cases diagnosed globally1 and 330,000 new cases anticipated in the United States in 2026.2 mCSPC is a form of advanced prostate cancer that has spread beyond the prostate but is still sensitive to androgen deprivation therapy.3 Approximately 5–10% of newly diagnosed cases are mCSPC,4,5 and up to 30% of these patients harbor HRR gene alterations.6

TALZENNA plus XTANDI in HRR gene-mutated mCSPC is an investigational treatment regimen. The results from TALAPRO-3 are being discussed with global health authorities to potentially expand the combination regimen’s existing indication. TALZENNA plus XTANDI is currently approved in more than 60 countries, including in the U.S. for adults with HRR gene-mutated mCRPC and in the European Union for adults with mCRPC in whom chemotherapy is not clinically indicated.

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ASCO (Free ASCO Whitepaper), which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.

About TALAPRO-3

The Phase 3 TALAPRO-3 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 599 patients with mCSPC (with ≤3 months of ADT [chemical or surgical] with or without an approved ARPI in the mCSPC setting) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients with histologically/cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell, or signet cell features and with alterations in one or more HRR genes (as per HRR12 gene panel) in the trial were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day.

The primary endpoint of the trial is investigator-assessed rPFS, defined as the time from the date of randomization to radiographic progression in soft tissue per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or in bone per Prostate Cancer Working Group 3 (PCWG3) criteria by investigator assessment, or death, whichever occurs first. Secondary endpoints include OS, objective response rate, duration of response, and patient-reported outcomes.

For more information on the TALAPRO-3 trial (NCT04821622), go to www.clinicaltrials.gov.

About TALZENNA (talazoparib)

TALZENNA is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.

TALZENNA was initially approved in the U.S., EU, and multiple other regions as a single agent for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer.

TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA in combination with XTANDI is approved in more than 60 countries, indications vary by country.

TALZENNA (talazoparib) Indication in the U.S.

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

HRR gene-mutated mCRPC:

In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Breast Cancer:

As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.
TALZENNA (talazoparib) Important Safety Information

WARNINGS and PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide. The durations of TALZENNA treatment in these 5 patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy.

Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.

Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia, have been reported in patients treated with TALZENNA. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 48%, 19%, and 9% of patients receiving TALZENNA and enzalutamide. Forty-two percent of patients (216/511) required a red blood cell transfusion, including 25% (127/511) who required more than one transfusion. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 8%, 3%, and 0.4% of patients.

Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics.

Embryo-Fetal Toxicity TALZENNA can cause fetal harm when administered to pregnant women. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 4 months following the last dose of TALZENNA.

ADVERSE REACTIONS

Serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%). Fatal adverse reactions occurred in 1.5% of patients, including pneumonia, COVID infection, and sepsis (1 patient each).

The most common adverse reactions (≥ 10%, all Grades), including laboratory abnormalities, for patients in the TALAPRO-2 study who received TALZENNA with enzalutamide vs patients receiving placebo with enzalutamide were hemoglobin decreased (79% vs 34%), neutrophils decreased (60% vs 18%), lymphocytes decreased (58% vs 36%), fatigue (49% vs 40%), platelets decreased (45% vs 8%), calcium decreased (25% vs 11%), nausea (21% vs 17%), decreased appetite (20% vs 14%), sodium decreased (22% vs 20%), phosphate decreased (17% vs 13%), fractures (14% vs 10%), magnesium decreased (14% vs 12%), dizziness (13% vs 9%), bilirubin increased (11% vs 7%), potassium decreased (11% vs 7%), and dysgeusia (10% vs 4.5%).

Clinically relevant adverse reactions in <10% of patients who received TALZENNA with enzalutamide included abdominal pain (9%), vomiting (9%), alopecia (7%), dyspepsia (4%), venous thromboembolism (3%) and stomatitis (2%).

DRUG INTERACTIONS

Coadministration with P-gp inhibitors The effect of coadministration of P-gp inhibitors on talazoparib exposure when TALZENNA is taken with enzalutamide has not been studied. Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a P-gp inhibitor.

Coadministration with BCRP inhibitors Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a BCRP inhibitor. Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure, which may increase the risk of adverse reactions.

USE IN SPECIFIC POPULATIONS

Males of Reproductive Potential Based on animal studies, TALZENNA may impair fertility.

Renal Impairment The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 – 59 mL/min) is 0.35 mg taken orally once daily with enzalutamide. The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 – 29 mL/min) is 0.25 mg taken orally once daily with enzalutamide. No dose adjustment is required for patients with mild renal impairment. TALZENNA has not been studied in patients requiring hemodialysis.

Please see full U.S. Prescribing Information and Patient Information for TALZENNA (talazoparib) at www.TALZENNA.com.

About XTANDI (enzalutamide)

XTANDI (enzalutamide) is an androgen receptor pathway inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 80 countries, including in the United States, European Union and Japan. Over 1.5 million patients have been treated with XTANDI globally.7

About XTANDI (enzalutamide) and Important Safety Information

XTANDI (enzalutamide) is indicated for the treatment of patients with:

castration-resistant prostate cancer (CRPC)
metastatic castration-sensitive prostate cancer (mCSPC)
nonmetastatic castration sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
Important Safety Information

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.

Interference with Immunoassay Measurement of Digoxin XTANDI can interfere with certain digoxin immunoassays (e.g., Chemiluminescent Microparticle Immunoassays), resulting in falsely elevated digoxin plasma concentration results. Notify the laboratory conducting the digoxin plasma concentration assay to use an appropriate method in patients receiving XTANDI and digoxin.

Adverse Reactions (ARs)

In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI. Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

Please access this link for XTANDI’S US Full Prescribing Information for additional safety information.

(Press release, Pfizer, MAY 30, 2026, View Source [SID1234666281])

On May 30, 2026 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company committed to developing first-in-class and best-in-class targeted cancer therapies, reported detailed efficacy and safety results from RINGSIDE, the global, randomized, double-blind, placebo-controlled Phase 3 trial of varegacestat in patients with progressing desmoid tumors. The data are being presented today in an oral abstract session at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago. Immunome submitted an NDA for varegacestat to the FDA in April 2026.

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"Desmoid tumors can be locally aggressive, painful and unpredictable, creating a high disease burden for patients and a continued need for new treatment options," said Mrinal M. Gounder, M.D., sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center, and the RINGSIDE primary investigator who is presenting the data. "The RINGSIDE data show a compelling progression-free survival benefit with varegacestat that is consistent across relevant patient subgroups, complemented by a high response rate and reduction in tumor volume. The data also show a rapid, clinically meaningful reduction in worst pain intensity, which is an important element for patients. These findings confirm varegacestat could become standard of care in the treatment of desmoid tumors."

"The detailed RINGSIDE data presented at ASCO (Free ASCO Whitepaper) reinforce varegacestat’s differentiated efficacy and manageable safety profile," said Clay Siegall, Ph.D., President and Chief Executive Officer of Immunome. "The depth and consistency of benefit observed across RINGSIDE point to varegacestat’s potential to deliver a meaningful advance for patients with desmoid tumors. These results form the basis for the NDA we submitted in April 2026 and the planned MAA submission for Europe."

RINGSIDE Key Clinical Data Presented at 2026 ASCO (Free ASCO Whitepaper) Meeting

As previously reported, the RINGSIDE trial met its primary endpoint and all key secondary endpoints. Varegacestat demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs. placebo, with an 84% reduction in the risk of disease progression or death (hazard ratio [HR] = 0.16, 95% confidence interval [CI]: 0.071, 0.375; p<0.0001). The PFS benefit observed with varegacestat vs. placebo was consistent across key subgroups, including tumor location, baseline tumor size, patient age and prior systemic desmoid tumor therapy.

As previously reported, the confirmed objective response rate (ORR) based on RECIST v1.1 was 56% with varegacestat vs. 9% with placebo (p<0.0001), as assessed by blinded independent central review. Among responders treated with varegacestat, median time to response was 8.2 months (range: 2.6–28.0 months) vs. 16.7 months (range: 8.1–30.2 months) for responders receiving placebo.

Varegacestat achieved a statistically significant improvement in change in worst pain intensity score at week 12, as assessed with the Gounder/Desmoid Tumor Research Foundation Desmoid Tumor Symptom/Impact scale. At week 12, patients treated with varegacestat experienced a mean change from baseline of -2.24 (standard error [SE]: 0.27) compared with +0.18 (SE: 0.27) for patients receiving placebo, for a treatment difference of -2.42 (SE: 0.37; p<0.0001). A clinically significant difference of more than 2 points was observed as early as the first evaluation at week 4.

Varegacestat achieved a statistically significant improvement in change in tumor volume at week 24, as assessed by blinded independent central review. At week 24, patients treated with varegacestat had a mean change from baseline of -109.6 (SE: 40.64) compared with +122.8 (SE: 42.72) for patients receiving placebo, for a treatment difference of -232.4 (SE: 57.39; p<0.0001). In a previously reported exploratory analysis, varegacestat demonstrated a median best change in tumor volume of -83% vs. +11% with placebo, also as assessed by blinded independent central review.

Varegacestat was generally well tolerated, with a manageable safety profile consistent with the gamma secretase inhibitor class. The most common adverse events for participants in the treatment arm as opposed to the placebo arm were diarrhea (82% vs. 27%), fatigue (44% vs. 23%), rash (43% vs. 12%), nausea (35% vs. 26%) and cough (34% vs. 5%). Most (95%) adverse events were grade 1 or 2. Among premenopausal women receiving varegacestat, 20 of 36 (56%) had ovarian toxicity adverse events, which resolved in 11 women (55%), and there were no discontinuations due to ovarian toxicity. Dose reductions due to treatment-emergent adverse events occurred in 80% of patients treated with varegacestat vs. 9% with placebo. Treatment discontinuations due to adverse events occurred in 20% of patients treated with varegacestat vs. 7% with placebo. The median exposure was 20.3 months for patients receiving varegacestat vs. 11.1 months for placebo.

Oral Presentation Details

Abstract Title

RINGSIDE: A phase 3 randomized, placebo-controlled trial of varegacestat for treatment of progressing desmoid tumors

Session Type/Title

Oral Abstract Session – Sarcoma

Date and Time

May 30, 2026, 5:00 p.m.–5:12 p.m. CDT

Presenter

Mrinal M. Gounder, M.D., Memorial Sloan Kettering Cancer Center

Abstract Number

11506

The slides from Dr. Gounder’s oral presentation will be available on the Immunome website in the "Presentations" page of the Investor Relations section.

Financial Disclosure

Dr. Gounder has financial interests related to Immunome.

About the RINGSIDE Trial

The global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial (ClinicalTrials.gov Identifier: NCT04871282) evaluated the efficacy and safety of varegacestat in patients with progressing desmoid tumors. A total of 156 patients were randomized to receive varegacestat 1.2 mg daily or placebo until disease progression or death, representing the largest randomized study in this population. The primary endpoint of the trial was progression-free survival as assessed by blinded independent central review. Statistically controlled secondary endpoints were confirmed ORR using RECIST v1.1 and change in tumor volume at week 24, both determined by blinded independent central review, as well as change in pain intensity at week 12 as determined using a patient-reported outcome instrument. Additional secondary endpoints included duration of response, best reduction in tumor volume, patient-reported outcomes, and safety and tolerability. RINGSIDE includes an open-label extension phase, which is ongoing.

About Desmoid Tumors

Desmoid tumors (also known as aggressive fibromatosis or desmoid-type fibromatosis) are aggressive non-metastatic soft tissue tumors that are prone to recurrence. Approximately 1,000-1,650 people are diagnosed with desmoid tumors each year in the United States, and there are approximately 10,000-11,000 actively managed patients. Those affected face debilitating pain, deformity and, in some cases, life-threatening organ damage. The chronic pain and physical limitations associated with desmoid tumors lead to a high clinical burden and impaired quality of life. Although desmoid tumors are not considered cancerous, they often require systemic treatment to prevent permanent disability and alleviate disease burden.

About Varegacestat

Varegacestat (formerly AL102) is an investigational, oral, once-daily gamma secretase inhibitor. In December 2025, Immunome reported positive topline results for the Phase 3 RINGSIDE trial of varegacestat in adults with progressing desmoid tumors. Immunome submitted an NDA to the FDA for varegacestat in April 2026 and plans to submit a Marketing Authorization Application to the European Medicines Agency for varegacestat by the end of 2026.

(Press release, Immunome, MAY 30, 2026, View Source [SID1234666280])