Teclistamab plus daratumumab in R/R Myeloma | Image Credit: 

Teclistamab-cqyv (Tecvayli) plus daratumumab and hyaluronidase-fihj 

 significantly improved overall survival (OS) and progression-free survival (PFS) vs standard daratumumab-based regimens in patients with 

multiple myeloma who had received 1 to 3 prior lines of therapy, according to findings from the phase 3 MajesTEC-3 trial (NCT05083169) presented at the 

The 36-month OS rate was 83.3% with the bispecific BCMA-directed CD3 T-cell engager teclistamab plus subcutaneous daratumumab (Tec-Dara) vs 65.0% with patients receiving investigator’s choice of subcutaneous daratumumab plus dexamethasone and either pomalidomide (DPd) or bortezomib (DVd).

Tec-Dara reduced the risk of death by 54% vs DPd/DVd (HR, 0.46; 95% CI, 0.32-0.65; 

At a median follow-up of 34.5 months, the median PFS had not been reached with Tec-Dara vs 18.1 months with DPd/DVd, translating to an 83% reduction in the risk of disease progression or death (HR, 0.17; 95% CI, 0.12-0.23; 

 <.0001). The 36-month PFS rates were 83.4% vs 29.7%, respectively.

The depth of response was also greater with Tec-Dara. The median duration of response was not yet evaluable for Tec-Dara compared with 23.5 months with DPd/DVd. Further, 81.8% of patients receiving Tec-Dara achieved a complete response or better compared with 31.1% of patients treated with DPd/DVd (

 <.0001). Among evaluable patients, the MRD negativity rate (10-5) was 89.3% vs 63.0%, respectively (

“MajesTEC-3 showed unprecedented efficacy, supporting a new second line and later standard of care with broad potential across academic and community settings,” said lead study author María-Victoria Mateos, MD, PhD, Hospital Universitario de Salamanca, Salamanca, Spain.

What were the safety data from the trial?

Teclistamab plus daratumumab demonstrated statistically siginificant improvements in both PFS and OS.

Teclistamab plus daratumumab achieved lower rates of discontinuation compared with daratumumab-based regimens.

The combination achieved deeper responses in patients compared with daratumumab-based regimens.

The safety profile for Tec-Dara showed that all cases of cytokine release syndrome were grade 1 (44.2%) or grade 2 (15.9%) and all cases were resolved.

The rate of immune effector cell-associated neurotoxicity syndrome was low with Tec-Dara at 1.1%. The most common hematologic adverse event (AE) with Tec-Dara was any grade neutropenia at 78.4% vs 82.8% with DPd/DVd. The most common nonhematologic AEs were infections, which occurred at grade 3/4 rates of 54.1% vs 43.4% in the Tec-Dara vs control arms, respectively.

Mateos noted that the rates of infections were much higher with Tec-Dara vs the control arm during the first 6 months; however, “beyond month 6, the incidence [of infections] was comparable, and what’s especially important is that the overall incidence of infection declined over time.”

Explaining the reason for the decrease in infections over time, Mateos said, “The study was initiated before the approval of teclistamab, when we did not yet have any peer-reviewed guidelines for the management of patients with bispecific monoclonal antibodies. When we observed this rate of infections, especially during the first 6 months, the trial protocol was amended and it was reinforced that investigators should use immunoglobulin replacement therapy and antimicrobial prophylaxis.”

At the time of the study analysis, 71% of patients remained on Tec-Dara. Fewer patients discontinued Tec-Dara at 4.6% vs 5.5% who discontinued DPd/DVd in the control arm. Fewer patients died in the Tec-Dara arm at 15.9% vs 33.1%, respectively.

The phase 3 MajesTEC-3 trial enrolled patients with R/R multiple myeloma who had received 1 to 3 prior lines of therapy including a proteosome inhibitor and lenalidomide (Revlimid). Patients who had received only 1 prior line had to be lenalidomide refractory per IMWG criteria, and all patients had to have an ECOG performance status of 0 to 2. Patients were not eligible to enroll if they had previously received BCMA-directed therapy or if they were refractory to anti-CD38 monoclonal antibodies.

Overall, 587 patients were randomized from October 22, 2021, to September 29, 2023. The median patient age was 65 years (range, 25-88) and the median number of prior lines of therapy was 2 (range, 1-3). There were 291 patients randomized to Tec-Dara and 296 patients randomized to DPd (n = 269) or DVd (n = 27).

Following the approved step-up dose schedule, patients in the experimental arm received teclistamab at 1.5 mg/kg weekly in cycles 1 and 2 followed by 3 mg/kg every 2 weeks in cycles 3 to 6 and 3 mg/kg every 4 weeks in cycle 7 onward. The cycles were 28 days. Subcutaneous daratumumab was administered at 1800 mg every week for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and every 4 weeks for cycles 7 onward. In the control arm, patients received investigator’s choice of DPd or DVd according to the approved schedules of the regimens. 

Commenting on the Tec-Dara regimen, Mateo said, “It's important to note that the combination of teclistamab plus daratumumab is a subcutaneous administration with a convenient monthly dosing after cycle 6, and the combination is free of steroids after cycle 1 day 8, and [this is all] extremely important from the patient perspective.”

The primary end point was PFS per IRC. Secondary end points included OS, response, MRD negativity, symptom score/quality of life, safety, and pharmacokinetics/immunogenicity.

Teclistamab is currently approved by the FDA for the treatment of adult patients with R/R multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. Blood. 2025;146(suppl 2): LBA-6. doi:10.1182/blood-2025-LBA-6

FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma. FDA. Published online October 25, 2022. Accessed December 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma

Articles

Teclistamab-cqyv combined with daratumumab and hyaluronidase-fihj significantly improved overall and progression-free survival in relapsed/refractory multiple myeloma patients compared to standard daratumumab-based regimens. The MajesTEC-3 trial demonstrated a 54% reduction in mortality risk and an 83% reduction in disease progression risk with the Tec-Dara regimen. The safety profile was manageable, with most adverse events being mild to moderate. The trial design included patients with 1-3 prior therapy lines, and the regimen offered a convenient dosing schedule, enhancing patient compliance and quality of life.

Teclistamab/daratumumab improved survival outcomes and led to deep MRD-negative responses vs daratumumab-based regimens in relapsed/refractory myeloma.

Teclistamab Plus Daratumumab Yields OS, PFS Benefit in R/R Multiple Myeloma

Non-Hodgkin Lymphoma | 
Image Credit: © Oleksandr 
- stock.adobe.com

The novel CD19-targeted CAR T-cell therapy GLPG5101 generated responses and displayed a manageable safety profile in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL), including mantle cell lymphoma (MCL), according to findings from the phase 1/2 ATALANTA-1 trial (NCT06561425).

Results from the MCL cohort were presented at the 

 by Marie Jose Kersten, MD, PhD, professor of hematology at Amsterdam UMC, on December 7, 2025.

The therapy showed high and durable antitumor activity across the studied NHL subtypes. In the R/R MCL patient cohort (n = 24), at 9.1 months’ median follow-up, all the patients achieved an overall response, and the complete response (CR) rate was 95.8%.

The therapy is distinguished by its use of a fresh, stem-like, early memory T-cell phenotype and a rapid, decentralized manufacturing platform that enables a 7-day vein-to-vein time.

Efficacy was evaluated in 42 patients who had reached the first response assessment. The objective response rate (ORR) was 88% (n = 37/42).

 The CR rate was 83% (n = 35/42). Of 11 responding patients in phase 1 of the study, 10 had an ongoing response at the data cutoff and 1 patient completed the study while in CR. In phase 2 of the study, all 21 patients had an ongoing response at the data cutoff. Of the total patients, 4 (3 with diffuse large B-cell lymphoma [DLBCL] and 1 with MCL) experienced progression after achieving an initial response.

GLPG5101 demonstrated robust expansion in the body across all tested dose levels and disease indications. Persistent CAR T-cells were detected in peripheral blood for up to 21 months post-infusion, indicating long-term durability.

Minimal residual disease (MRD) negativity in plasma was achieved in 12 of 15 (80%) evaluable patients who had achieved a CR. Crucially, all 11 MRD-negative patients with a minimum of 6 months follow-up remained in ongoing CR at the time of data cutoff, linking deep molecular remission to durable clinical benefit.

In the R/R MCL cohort, 90% (n = 9/10) of MRD-evaluable patients were MRD-negative at CR. Additionally, 7 of the 9 MRD-negative patients remained in CR at the time of the data cutoff.

GLPG5101 produced responses and had a manageable safety profile in R/R NHL, including MCL.

At a median follow-up of 9.1 months, the ORR in the MCL cohort was 100%, including a CR rate of 95.8%.

GLPG5101 previously received FDA regenerative medicine advanced therapy designation for MCL.

GLPG5101 demonstrated a manageable safety profile with low incidence of high-grade toxicities in the MCL cohort. The reported data reflects treatment-emergent adverse effects (TEAEs) reported up to 14 weeks post-infusion.

In phases 1 and 2, any grade cytokine release syndrome (CRS) occurred in 9 vs 10 patients. Grade 3 or higher CRS occurred in 1 vs 0 patients. Any grade immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 6 vs 4 patients, and grade 3 or higher ICANS occurred in 0 vs 1 patients.

The most frequently reported TEAEs of grade 3 or higher were hematologic. Out of 49 infused patients, 2 died during the treatment period, and 1 died during follow-up.

This is an ongoing phase 1/2 study designed to evaluate the safety and efficacy of GLPG5101.

The primary objectives of phases 1 and 2 are to establish the safety, determine the recommended phase 2 dose, and to evaluate the efficacy of GLPG5101. The secondary objectives are to assess manufacturing feasibility, further safety parameters, and additional efficacy metrics such as duration of response and MRD.

The ATALANTA-1 trial enrolled heavily pretreated adult patients with various subtypes of R/R NHL. Patients had a median of 2 prior systemic therapies. Eligible indications included DLBCL, MCL, follicular lymphoma, marginal zone lymphoma, Burkitt lymphoma, and primary central nervous system lymphoma.

In the MCL cohort, the median age of patients in phase 1 was 66.5 years (range, 25–78), and 67 years (range, 40–81) in phase 2. The median range of prior therapies between both phases was 2.5 (range, 1–7) vs 3 (range, 2–11). The majority of patients had received prior Bruton tyrosine kinase inhibitor.

As of the data cutoff, 53 patients had undergone leukapheresis, 49 received an infusion, and 47 of the 49 patients received fresh product. In the R/R MCL cohort, 25 patients received CAR T-cell infusion, with 24 patients receiving fresh product.

A 7-day vein-to-vein time was successfully achieved in 43 of the 47 patients (91%) who received the fresh product. In the R/R MCL cohort specifically, 23 of 24 patients achieved a 7-day vein-to-vein time. Short vein-to-vein time eliminated the need for cytotoxic bridging therapy for all patients who received a fresh product.

The final product demonstrated significant enrichment of desired T-cell phenotypes compared to the starting material. The proportion of early T-cell phenotypes (naive/stem cell memory and central memory) was significantly increased in both CD4+ and CD8+ CAR T cells. A median increase in the CD4:CD8 ratio of CAR+ T cells was observed in the final product.

In August 2025, GLPG5101 received a regenerative medicine advanced therapy designation in MCL from the FDA based on preliminary clinical data.

The interim results from the ATALANTA-1 study provide strong evidence for the potential of GLPG5101 as a novel CAR T-cell therapy for R/R NHL. The rapid, 7-day vein-to-vein manufacturing time is a significant logistical advantage that can accelerate access to treatment for patients with urgent clinical needs.

“In conclusion, in the ATALANTA-1 study, we saw deep and durable responses in patients with MCL, including patients with high-risk features, of course with relatively short follow-up,” concluded Kersten during the presentation.

 “And we saw…a 96% CR in patients with high-risk disease and a duration of response at 9 months of 83%. We have a very favorable safety profile, no grade 3 or higher CRS and only 1 patient with grade 3 ICANS. We would feel very comfortable even in [patients with MCL] to deliver this therapy on an outpatient basis…All in all, we think this product should be further developed.”

Kersten M, Vermaat J, Mutsaers P, et al. High complete response rates and minimal residual disease (MRD) negativity, with durable responses, in high-risk mantle cell lymphoma (MCL) with GLPG5101, a fresh, early memory-enriched CAR T-cell therapy with a 7-day vein-to-vein time: Results from the ATALANTA-1 MCL cohort. Presented at: 2025 ASH Annual Meeting; December 7, 2025; Orlando, Florida. Abstract 662.

Kersten M, Saevels K, Willems E, et al. ATALANTA-1: A phase 1/2 trial of GLPG5101, a fresh, stem-like, early memory CD19 CAR T-cell therapy with a 7-day vein-to-vein time, for the treatment of relapsed/refractory non-Hodgkin lymphoma. 

. 2024;144(suppl 1):93. doi:10.1182/blood-2024-205360.

GLPG5101, a novel CD19-targeted CAR T-cell therapy, has shown promising results in patients with relapsed/refractory non-Hodgkin lymphoma, including mantle cell lymphoma, as demonstrated in the ATALANTA-1 trial. The therapy achieved high overall and complete response rates, with durable antitumor activity and manageable safety profile. The rapid 7-day vein-to-vein manufacturing process is a significant advantage, eliminating the need for bridging therapy. The study highlights the potential of GLPG5101 as an effective treatment option, particularly for high-risk patients, with favorable safety outcomes.

GLPG5101 produced responses and had a manageable safety profile in relapsed/refractory non-Hodgkin lymphoma, including mantle cell lymphoma.

GLPG5101 Produces Responses With Manageable Safety in R/R NHL, MCL

Saruparib plus an ARPI in metastatic prostate cancer:

Saruparib in combination with an androgen receptor pathway inhibitor (ARPI) was safe and effective for the treatment of patients with metastatic prostate cancer, according to data from the phase 1/2 PETRANHA trial (NCT05367440).

Data from the efficacy-evaluable population presented during the 

 showed that objective response rates were 88.5% (23/26) in patients with metastatic castration-sensitive prostate cancer (mCSPC), 25% (2/8) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had prior ARPI, and 73.3% (11/15) in patients with ARPI-naive mCRPC. Rates of prostate specific antigen (PSA) reduction >90% were 100%, 5.6%, and 53.3% in the 3 groups, respectively, and rates of undetectable PSA (<0.2 ng/mL), were 83.3%, 5.3%, and 29.0%, respectively.

“Saruparib plus ARPI has promising safety and preliminary efficacy in patients with mCSPC and ARPI-naïve mCRPC,” first study author Arun A. Azad, MBBS, FRACP, PhD, Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, said when presenting the data at ESMO. “Exploratory analyses demonstrated PSA responses in pts irrespective of whether their tumor harbored an HRRm or not,” added Azad.

What was the safety profile of saruparib?

Across the overall population, the median duration of exposure to saruparib was 12.8 months (range, 0.2-28.2). The median duration of saruparib exposure among patients with mCSPC, mCRPC and prior ARPI, and ARPI-naive mCRPC was 17.8 months (range, 0.2-28.2), 5.5 months (range, 1.2-17.7), and 14.7 months (range, 0.3-24.8), respectively. The median exposure to ARPI in these 3 groups was 19.7 months (range, 0.2-28.2), 5.5 months (range, 1.1-17.7), and 15.7 months (range, 0.4-24.8), respectively.

Among the mCSPC, prior ARPI mCRPC, and ARPI-naive mCRPC groups, any grade adverse events (AEs) occurred at rates of 96.3%, 94.7%, and 100%, respectively. AEs specifically related to saruparib occurred at rates of 85.2%, 84.2%, and 90.3%, respectively. Grade ≥3 AEs were experienced by 51.9%, 31.6%, and 51.6% of the 3 groups, respectively, and serious AEs were reported in 14.8%, 21.1%, 32.3% of patients, respectively.

Across the entire population, AEs led to saruparib discontinuation in 10.4% of patients. AE-related discontinuation of saruparib and ARPI occurred in 11.1% and 3.7% of mCSPC patients, respectively, 5.3% and 5.3% of prior-ARPI mCRPC patients, and 12.9% and 3.2% of ARPI-naive mCRPC patients. AE-related dose reductions of saruparib and ARPI occurred in 29.6% and 0% of mCSPC patients, respectively, 26.3% and 21.1% of prior-ARPI mCRPC patients, and 35.5% and 12.9% of ARPI-naïve mCRPC patients.

Lastly, AE-related treatment interruption of saruparib and ARPI occurred in 51.9% and 44.4% of mCSPC patients, respectively, 36.8% and 31.6% of prior-ARPI mCRPC patients, and 67.7% and 51.6% of ARPI-naïve mCRPC patients.

What was the study design and rationale for the PETRANHA trial?

The rationale for the phase 1/2 PETRANHA trial was to explore the potential of improving upon the established metastatic prostate cancer treatment of combination therapy with a PARP inhibitor and ARPI for selected patients with mCRPC. The researchers were specifically evaluating whether combining a PARP1-selective inhibitor, such as saruparib, could enhance efficacy and safety outcomes compared with the standard approach of combining a non-selective PARP inhibitor with ARPI.

The study design had patients assigned by investigator choice to 1 of 4 treatment arms defined by the ARPI used. Patients in the analysis presented at ESMO received 60 mg of saruparib once daily combined with enzalutamide (Xtandi) at 160 mg once daily (Arm 1; n = 18), abiraterone acetate (Zytiga) at 1000 mg once daily plus 5 mg of prednisone once daily (Arm 2; n = 23), or darolutamide (Nubeqa; n = 36) at 600 mg twice daily (Arm 3). Data from arm 4 of the study, in which patients are receiving saruparib at the same dose plus apalutamide (Erleada) at 240 mg once daily, were not available for this analysis.

All treatment is being administered until disease progression or intolerable toxicity. The primary end points are safety and tolerability, with efficacy outcomes being the secondary end points.

What were the patient characteristics of the PETRANHA trial?

At the data cutoff of October 28, 2024, the phase 1/2 PETRANHA trial included 77 patients with metastatic prostate cancer. Of these patients, 65% (n = 50) had mCRPC and 35% (n = 27) had mCSPC. A little over one-third (n = 19) of the mCRPC population had previously received ARPI and about two-thirds (n = 31) were ARPI-naive. Across the whole population, 20.8% (n = 16) had tumors harboring a homologous recombination repair mutation.

What are the next steps with saruparib in metastatic prostate cancer?

The ongoing, double-blinded, randomized phase 3 EvoPAR-PR01 trial (NCT06120491) is comparing saruparib vs placebo, both given in combination with physician’s choice of ARPI in patients with mCSPC.

 The study will explore this comparison in both populations of patients with HRR mutations (550 patient target) and those without mutations (1250 patient target). The primary outcome measure is radiographic progression-free survival (PFS) and key secondary outcomes measures are overall survival, PFS2, and symptomatic skeletal event–free survival.

: Azad declared associations with following companies: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, Bristol Myers Squibb, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dohme, Daiichi Sankyo, Arvinas; Financial Interests, Personal, Other, Consultant: Aculeus Therapeutics; Exelixis; Aptevo , Hinova, Glaxo Smith Kline, SYNthorx, Bionomics, Lilly, Gilead Sciences.

Azad AA, Joshua AM, Voskoboynik M, et al. First interim efficacy analysis of the phase I/II PETRANHA trial of saruparib + androgen receptor pathway inhibitors (ARPI) in patients (pts) with metastatic prostate cancer (mPC). Presented at: ESMO 2025 Congress; October 17-20, 2025; Berlin, Germany. Abstract 2384MO.

Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents (EvoPAR-PR01). ClinicalTrials.gov. Last updated October 10, 2025. Accessed October 17, 2025. https://clinicaltrials.gov/study/NCT06120491

Saruparib combined with an androgen receptor pathway inhibitor (ARPI) demonstrated safety and efficacy in treating metastatic prostate cancer, as shown in the phase 1/2 PETRANHA trial. The trial reported high objective response rates in patients with metastatic castration-sensitive prostate cancer (mCSPC) and ARPI-naive metastatic castration-resistant prostate cancer (mCRPC). Adverse events were common but manageable, with some leading to treatment discontinuation. The trial's design aimed to improve outcomes by using a PARP1-selective inhibitor. Future research will further explore saruparib's efficacy in a phase 3 trial.

Saruparib plus an androgen receptor pathway inhibitor was safe and active in metastatic prostate cancer.

Saruparib Plus an ARPI Shows Activity, Tolerability in Metastatic Prostate Cancer

Image by Ashling Wahner and MJH Life Sciences Using AI

177-Lu-edotretide (ITM-11) led to a significant improvement in progression-free survival (PFS) compared with everolimus (Afinitor) for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), meeting the primary end point of the phase 3 COMPETE trial (NCT03049189), according to data from the study presented during the 

The median PFS per central assessment was 23.9 months (95% CI, 18.7-30.0) vs 14.1 months (95% CI, 9.2-20.9) in the ITM-11 vs everolimus arms, respectively (HR, 0.67; 95% CI, 0.48–0.95; 

 = .022). Median PFS per local assessment was 24.1 months (95% CI, 21.2-26.7) vs 17.6 months (95% CI, 12.2-21.0), respectively (HR, 0.66; 95% CI, 0.48-0.91; 

The secondary end point of the trial was overall survival (OS), which was also identified to be higher in patients who were given ITM-11 vs everolimus.

There was a total of 207 patients in the ITM-11 group and 102 patients in the everolimus group, respectively. The median ages of both groups were 65 (ITM-11), and 61 (everolimus). The majority of patients in both groups were male (531.1% vs 56.9%). The majority of patients had grade 2, non-functional GEP-NETs (83.2% vs 86.4%) and had received prior therapy (85.5% vs 83.3%).

What Were the Additional Results of the COMPETE Trial?

In the subgroup analysis of PFS by tumor origin, median PFS was found to be numerically longer for GE-NETs and P-NETs in the ITM-11 arm. For GE-NETs, the median PFS was 23.9 months (14.0-not evaluable [NE]) vs 12.0 months (95% CI, 8.8-23.7; HR, 0.64; 95% CI, 0.38- 1.08; 

 = .090). For P-NETs, the median PFS was 24.5 months (18.4-30.0) vs 14.7 months (95% CI, 8.5-NE; HR, 0.70; 95% CI, 0.45-1.09; 

It was also identified that median PFS was numerically longer in grade 1 and significantly longer in grade 2 tumors in the ITM-11 arm. Grade 1 had a median PFS of 30.0 months (95% CI, 9.5-NE) vs 23.7 months(95% CI, 12.0-NE; HR, 0.89; 95% CI, 0.42-1.8; 

 =.753), and grade 2 had a median PFS of 21.7 months (95% CI, 18.6-29.9) vs 9.2 months (95% CI, 8.5-18.1; HR, 0.55l; 95% CI, 0.37-0.82; 

PFS was also assessed by prior therapy; it was identified that median PFS was numerically longer in the first line and significantly longer in the second line in the ITM-11 arm. First line data showed the median PFS was not reached in the ITM-11 arm vs 18.1 months (95% CI, 4.4-NE) in the everolimus arm (HR, 0.60; 95% CI, 0.25-1.45; 

 = .249), and second line data showed the median PFS of 23.9 months (95% CI, 18.2-29.9) vs 14.1 months (95% CI, 9.2-21.0; HR, 0.68; 95% CI, 0.47-0.98; 

Overall response rates (ORR), one of the secondary end points of the trial, were found to be significantly higher in the ITM-11 arm. Central assessment showed an ORR of 21.9% vs 4.2% (

<.0001) between both arm, with complete responses (CR) being 1.9% vs 0.0%, partial response (PR) of 19.3% vs 3.9%, stable disease of 59.4% vs 72.5%, progressive disease of 16.4% vs 16.7%, and no post-baseline CT data available or missing in 2.9% vs 6.9%. For local assessment, the ORR was 30.5% vs 8.4% (

<.0001) with a CR of 0.0% vs 1.0%, PR of 30.0% vs 6.9%, stable disease of 58.9% vs 72.5%, progressive disease of 9.2% vs 12.7%, and no post-baseline CT data available or missing in 1.9% vs 6.9% .

Adverse events (AEs) related to the drug study were experienced by 82% of patients ITM-11 group, and 97% of patients in the everolimus group. The most common AEs reported were nausea (30% vs 10.1%), diarrhea (14.3% vs 35.4%), asthenia (25.3% vs 31.3%), and fatigue (15.7% vs 15.2%). These AEs were expected based on the known safety profile of ITM-11.

AEs leading to premature study discontinuation occurred in 1.8% vs 15.2% of patients between the groups, respectively. Dose modification or discontinuation occurred in 3.7% vs 52.5% of patients among both groups, and the number of patients with delayed study drug administration due to toxicity was 0.9% in the ITM-11 group and not available in the everolimus group.

Dosimetry data showed targeted tumor uptake with low exposure to healthy organs, with normal organ absorbed doses well below safety thresholds.

Patient inclusion criteria included being 18 or older; having well-differentiated, non-functional GE-NET or functional/non-functional P-NET; grade 1/2 unresectable or metastatic, progressive, SSRT-positive+ disease; or being treatment-naive to first-line therapies or progressing, or progressing under prior second-line therapies.

Morphologic imaging was conducted in 3-month intervals. The PFS follow-up was done every 3 months after the first 30 days. Long-term follow-up was done every 6 months.

“With these data combining extensive dosimetry information from more than 200 patients included in a prospective trial, ITM is laying the groundwork for improved therapeutic decision-making by providing important insights into tumor uptake and treatment variability,” Emmanuel Deshayes, MD, PhD, professor in biophysics and nuclear medicine at the Montpellier Cancer Institute in France, said in a news release.

 “It may offer clinically meaningful implications for optimizing individualized patient management.”

Dosimetry data from COMPETE shaped the design of ITM’s phase 3 COMPOSE (NCT04919226)

 trial, with ITM-11 in well-differentiated, aggressive grade 2 or grade 3 SSTR-positive+ GEP-NET tumors, as well as the upcoming phase 1 pediatric KinLET (NCT06441331) study in SSTR-positive+ tumors.

Capdevila noted grants and/or research support from Advanced Accelerator Applications, AstraZeneca, Amgen, Bayer, Eisai, Gilead, ITM, Novartis, Pfizer, and Roche; participation as a speaker, consultant, or advisor for Advanced Acclerator Applications, Advanz Pharma, Amgen, Bayer, Eisai, Esteve, Exelixis, Hutchmed, Ipsen, ITM, Lilly, Merck Serono, Novartis, Pfizer, Roche, and Sanofi; position as advisory board member for Amgen, Bayer, Eisai, Esteve, Exelixis, Ipsen, ITM, Lilly, Novartis, and Roche; and a leadership role and chair position for the Spanish Task Force for Neuroendocrine and Endocrine Tumours Group (GETNE).

1.Capdevilla J, Amthauer H, Ansquer C, et al. Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase 3 COMPETE trial. Presented at: 2025 ESMO Congress; October 17-20, 2025; Berlin, Germany. Abstract 1706O

2. ITM presents dosimetry data from phase 3 COMPETE trial supporting favorable efficacy and safety profile with n.c.a. 177Lu-edotreotide (ITM-11) in patients with gastroenteropancreatic neuroendocrine tumors at EANM 2025 Annual Congress. News release. ITM. October 8, 2025. Accessed October 18, 2025. https://tinyurl.com/3nuscs4m

3. Lutetium 177Lu-Edotreotide versus best standard of care in well-differentiated aggressive grade-2 and grade-3 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) – COMPOSE (COMPOSE). ClinicalTrials.gov. Updated September 10, 2025. Accessed October 18, 2025. https://www.clinicaltrials.gov/study/NCT04919226

4. Phase I trial to determine the dose and evaluate the PK and safety of lutetium Lu 177 edotreotide therapy in pediatric participants with SSTR-positive tumors (KinLET). ClinicalTrials.gov. Updated September 19, 2025. Accessed October 18, 2025. https://www.clinicaltrials.gov/study/NCT06441331

177-Lu-edotretide (ITM-11) demonstrated a significant improvement in progression-free survival (PFS) compared to everolimus in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in the phase 3 COMPETE trial. The trial showed a median PFS of 23.9 months for ITM-11 versus 14.1 months for everolimus. Secondary endpoints, including overall survival and overall response rates, favored ITM-11. Adverse events were more common in the everolimus group. Dosimetry data indicated targeted tumor uptake with low exposure to healthy organs, supporting the safety and efficacy of ITM-11.

177-Lu-edotretide significantly improved survival outcomes vs everolimus for the treatment of patients with grade 1/2 GEP-NETs.

177-Lu-edotretide Prolongs PFS Compared With Everolimus in Grade 1/2 GEP-NETs

Image credit: Sebastian Kaulitzki - stock.adobe.com

Induction and maintenance therapy with durvalumab (Imfinzi) combined with BCG produced a statistically significant and clinically meaningful disease-free survival (DFS) improvement compared with BCG alone in patients with BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC), according to results from the phase 3 POTOMAC trial (NCT03528694) that were presented at the 

The findings were presented by Maria De Santis, MD, associate professor at the University of Warwick Medical School in Coventry, England, and simultaneously published in 

The open-label, randomized study was made up of 1-018 patients who were randomized 1:1 in 3 cohorts: 339 received 1 year of durvalumab in combination with BCG induction and maintenance therapy, 339 received 1 year of durvalumab with BCG induction only, and 340 received only BCG and induction and maintenance therapy.

The primary endpoint of DFS was achieved, with a 32% reduction in risk of a DFS event (HR 0.68; 95% CI, 0.50–0.93; 

=.0154) with the addition of durvalumab to BCG induction and maintenance. Early and sustained DFS benefit with duravalumab was observed starting as early as 4 months (HR 0.68; 95% CI, 0.50-0.93; 

=.0154). The median follow-up was 60.7 months.

However, the different in DFS for durvalumab plus BCG induction only vs BCG induction and maintenance was not statistically significant (HR, 1.14; 95% CI, 0.86–1.50; 

 =.3530). While overall survival (OS) data were immature, there was no detriment to OS with the addition of durvalumab to BCG and induction and maintenance therapy (HR 0.80; 95% CI, 0.53–1.20).

The addition of durvalumab to BCG and induction and maintenance therapy had no major impact on patient-reported quality of life, one of the secondary endpoints of the trial.

Regarding safety, another key secondary end point, the results showed that the durvalumab/BCG regimen was tolerable and manageable with no unexpected toxicities, and there were no deaths possibly related to the study treatment reported. Grade 3 or 4 AEs possibly related to any treatment were reported in 21% of the durvalumab/BCG induction and maintenance arm, 15% of the durvalumab/BCG induction arm, and 4% of the BCG induction and maintenance arm.

The most frequently reported any-grade AEs in the durvalumab/BCG induction and maintenance and BCG-only arms included dysuria (37% vs 36%, respectively), hematuria (32% vs 30%), pollakiuria (26% vs 25%), urinary tract infection (21% vs 18%), cystitis (19%vs 19%), and pyrexia (16%vs 20%).

“Overall, these events were consistent with what we expected for durvalumab and BCG therapy with dysuria, hematuria, and pollakiuria being the 3 most commonly reported in both arms,” said De Santis during the presentation.

Majority of the patients were male, and the median age was 68. Approximately 64% of patients had papillary disease only. Patients also had high-risk tumors, defined as being either T1, high grade, carcinoma in situ, or multiple and recurrent and large.

Patients received a median of 6 BCG induction instillations and 14 BCG maintenance instillations, with a maximum of 15 in both arms. More than half of patients received BCG for 18 months.

“In conclusion, POTOMAC supports 1 year of durvalumab with BCG and induction and maintenance therapy as a potential new treatment in BCG-naive, high-risk NMIBC,” De Santis said during the presentation.

 De Santis declared a consulting or advisory role with AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, Bristol Myers Squibb, Eisai, Ferring, Gilead Sciences, Immunomedics, Ipsen, Janssen, Merck Sharp & Dohme, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, SeaGen, and Thermosome.

Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer (POTOMAC). ClinicalTrials.gov. Updated August 27, 2025. Accessed October 17, 2025. https://clinicaltrials.gov/study/NCT03528694

De Santis M. Durvalumab (D) in Combination With Bacillus Calmette-Guerin (BCG) for BCG-Naive, High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC): Final Analysis of the Phase 3, Open-Label, Randomized POTOMAC Trial. Presented at: ESMO 2025 Congress; October 17-20, 2025; Berlin, Germany. Abstract LBA108.

De Santis M, Redorta J, Nishiyama H, et al. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. 

Published online ahead of print October 17, 2025. Doi: 10.1016/S0140-6736(25)01897-5

Induction and maintenance therapy with durvalumab combined with BCG significantly improved disease-free survival (DFS) in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC) patients compared to BCG alone, as demonstrated in the phase 3 POTOMAC trial. The study involved 1,018 patients and showed a 32% reduction in DFS event risk with durvalumab addition. The treatment was well-tolerated with manageable side effects and no unexpected toxicities. Quality of life remained unaffected, and overall survival data were immature but showed no detriment with durvalumab addition.

Durvalumab plus BCG induction and maintenance therapy yielded clinically meaningful improvement in DFS vs BCG induction and maintenance therapy alone in BCG-naive, high-risk NMIBC.

Paige Britt

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