Jason M Broderick

Currently, Jaypirca is approved by the FDA for patients with relapsed or refractory CLL/SLL who have already been treated with another BTK inhibitor.

Jaypirca (pirtobrutinib) was found to have similar efficacy as Imbruvica (ibrutinib) in improving clinical efficacy in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These positive findings came from the phase 3 BRUIN CLL-314 trial (NCT05254743), which compared the two drugs head-to-head in both patients who had never before received a BTK inhibitor, a specific type of targeted therapy, as well as those with relapsed/refractory disease. 

The results, presented by Dr. Jennifer Woyach at the 

, also showed that Jaypirca showed a promising trend toward better long-term control of the disease.

The study looked at two main groups of patients: those who were newly diagnosed, known as treatment naive, and those whose disease had come back or resisted previous treatment, known as relapsed/refractory. Overall, 662 patients were randomly assigned to receive either Jaypirca or Imbruvica.

In all patients treated, the objective response rate (ORR) for Jaypirca was 87% compared with 78.5% for Imbruvica. This demonstrated that Jaypirca was noninferior, or not worse than, Imbruvica, and also showed consistently higher response rates across all patient groups. The best response (complete response [CR] or CR with incomplete blood recovery) was achieved by 4.8% of patients on Jaypirca versus 2.4% on Imbruvica.

Woyach noted that Jaypirca showed a higher ORR in both the treatment-naive population (92.9% vs. 85.8%) and the relapsed/refractory population (84.0% vs. 74.8%).

While it is still early, data on progression-free survival (PFS) — the time patients live without their disease worsening — showed a trend favoring Jaypirca.

In all patients studied, the percentage of patients alive without their disease progressing at eighteen months was 86.9% for Jaypirca versus 82.3% for Imbruvica.

At eighteen months, 95.3% of newly diagnosed patients on Jaypirca were alive without their disease progressing, compared with 87.6% of those on Imbruvica.

Woyach explained that this early trend in PFS was most pronounced in the treatment-naive group, where patients have been followed for the longest period.

Jaypirca was generally well tolerated by patients, with fewer patients needing to reduce their dose or stop the drug due to side effects compared with Imbruvica.

Atrial fibrillation/flutter occurred at a rate of 2.4% with Jaypirca, which was substantially lower than the 13.5% seen with Imbruvica. This difference was even greater in patients aged 75 or older (4.5% with Jaypirca vs. 21.4% with Imbruvica).

Common side effects of any grade for Jaypirca included low white blood cell count, upper respiratory infections, anemia, and pneumonia.

Rates of hypertension were also lower with Jaypirca compared with Imbruvica.

BRUIN CLL-314 is the first to directly compare Jaypirca and Imbruvica in patients who have not previously received a BTK inhibitor.

Woyach noted that as the PFS data continue to mature and uphold the trend favoring Jaypirca, these findings will support a request to the FDA to use the drug as a first-line treatment for CLL/SLL.

1. "Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor" by Jennifer Woyach et al., 

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Jaypirca (pirtobrutinib) demonstrated comparable efficacy to Imbruvica (ibrutinib) in treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to the phase 3 BRUIN CLL-314 trial. The study included treatment-naive and relapsed/refractory patients, showing higher objective response rates (ORR) for Jaypirca. Progression-free survival (PFS) trends favored Jaypirca, especially in treatment-naive patients. Jaypirca was well tolerated, with fewer dose reductions and lower atrial fibrillation rates compared to Imbruvica. These findings may support FDA approval for Jaypirca as a first-line treatment for CLL/SLL.

A clinical trial found that Jaypirca was more effective than Imbruvica across the frontline and relapsed/refractory CLL/SLL settings.

Jaypirca Matches Imbruvica's Effectiveness for CLL, With Hints of Long-Term Benefit

Among patients with previously untreated diffuse large B-cell lymphoma, odronextamab has been associated with early efficacy.

Amog patients with previously untreated diffuse large B-cell lymphoma (DLBCL), treatment with the CD20 and CD3 bispecific antibody odronextamab has been associated with early efficacy in combination with standard CHOP chemotherapy.

The first results from a small cohort of patients enrolled in part 1 of the phase 3 OLYMPIA-3 study were presented at the 2025 ASH Annual Meeting.

In the early results, the objective response rate (ORR) was 78% with the weekly 80 milligram dose of odronextamab plus CHOP and was 100% for the weekly 160 milligram dose of odronextamab plus CHOP. The complete response rates were 44% and 100% for each dose, respectively. The median duration of response, duration of complete response and progression-free survival were not yet reached at the early analysis. Based on the combination of efficacy and safety, the 160 milligram dose of odronextamab was selected for further investigation in the randomized portion of the study comparing the bispecific with Rituxan (rituximab).

Objective Response Rate (ORR): the percentage of patients whose tumors shrink or disappear after treatment. 

Progression-Free Survival (PFS): the length of time during and after treatment when the cancer does not grow or spread. 

ECOG Performance Status: a scale doctors use to describe how well a person is able to perform daily activities. 

Neutropenia: a drop in neutrophils, a type of white blood cell that fights infection. 

Cytokine Release Syndrome (CRS): a reaction that can happen when the immune system becomes very active during certain treatments, like immunotherapy. Symptoms may include fever, fatigue, or low blood pressure.

Anemia: a condition in which the body has too few red blood cells. 

"Data from part 1a of OLYMPIA-3 suggest that when combining odronextamab with CHOP in previously untreated patients with DLBCL, [Rituxan] was not required to achieve deep and durable responses," lead investigator Dr. Jean-Marie Michot from Institute Gustave Roussy, said during a presentation of the results. "The safety profile of fixed duration odronextamab-CHOP treatment was generally manageable in patients with previously untreated DLBCL with high-risk features, with no new safety signals compared with previous reports."

OLYMPIA-3 Study Design and Patient Characteristics

The open-label study was designed with two parts. In part 1, the dose of odronextamab was escalated and optimized. Standard CHOP was given on day 1 and 8 of each cycle and odronextamab was administered starting on day 8, initially at a step-up dose of 0.7/4/20 milligrams and then at varying dose levels including 80 milligrams or 160 milligrams weekly and 160 milligrams and 320 milligrams every two weeks, with data only available for the weekly doses. Part 2 of the study will continue CHOP with patients randomly assigned to receive odronextamab (Odro-CHOP) or Rituxan(R-CHOP).

Across all of part 1, the median age of patients was 66 years, with nearly a third aged 75 or older (32%). ECOG performance status was 0 (40%), 1 (45%) and 2 (14%). The primary cell of origin was non-GCB (59%), and all patients had de novo DLBCL. IPI score was 3 for 36% and 4 to 5 for 27% of patients. The Lugano stage was 3 to 4 for 95% of patients.

At the time of the analysis, 77.8% of patients enrolled to the 80 milligram dose had completed cycle 1 to 6 (seven of nine). The remainder of patients in this group had discontinued early, due to physician decision (two patients). In the 160-mg arm (13 patients), all patients had completed cycle 1 and 84.6% had completed cycle 6. Two discontinued early due to physician decision. The relative dose intensity was 87% in the 80-milligram group and 77% in the 160- milligram group.

"Most patients completed six cycles of odronextamab-CHOP at both dose levels," said Michot. "There were few dose reductions of odronextamab and no permanent treatment discontinuations due to [treatment-emergent side effects] related to odronextamab. There were no clinically important differences in safety between dose levels."

Additional Odronextamab Efficacy Findings

The median duration of follow-up was 9.2 months for those enrolled in the 80 milligram dose and was 7.8 months for those in the 160 milligram dose. At the assessment, most responses remained ongoing. "CRs appeared durable," Michot said.

In a biomarker analysis, B cell counts declined quickly following the initiation of therapy. There was an initial drop with CHOP administration, with B cells being completely cleared with the initiation of odronextamab.

There was slight T cell margination following the initiation of therapy, but these were transient and like prior reports with odronextamab, Michot said. T cell findings were similar for each dose.

Grade 3 (severe) or higher treatment emergent side effects were experienced by all patients treated with the 80 milligram and 160 milligram doses of odronextamab. Serious treatment emergent side effects were seen in 77.8% of those treated with the 80 milligram dose and for 92.3% of those administered the 160 milligram dose. Treatment emergent side effects led to treatment interruption or delay for 66.7% of those in the 80-milligram arm and for 84.6% of those in the 160-milligram group.

Treatment emergent side effects led to an odronextamab dose reduction for no patients in the 80 milligram arm and for one in the 160-milligram group. Dose reductions in CHOP due to treatment emergent side effects were needed for one patient in the 80-milligram group and for five in the 160-milligram group. Treatment emergent side effects led to treatment discontinuation for one patient in each dose level arm. There was one treatment emergent side effect that led to death in the 160-milligram arm. "Of note, there were no dose-limiting toxicities reported," Michot said.

Across both doses, the most common treatment emergent side effects were neutropenia (81.8%), cytokine release syndrome (CRS; 54.5%), anemia (45.5%) and nausea (40.9%). The most common treatment-related side effects were similar with neutropenia seen in 77.3% of patients, CRS in 54.5%, anemia in 45.5% and nausea in 36.4%.

CRS was solely grade 1 (mild)/2 (moderate) in severity, with 40.9% of patients having a grade 1 event and 13.6% having a grade 2 event. Tocilizumab was administered to manage CRS for 27.3% of patients and steroids were given for 18.2%. The median CRS duration was 3.8 months and the median time to onset was nine hours. CRS mostly occurred during the step-up dosing phase at the lowest dose of 0.7 mg, after this initial step-up the rates of CRS were low. There were no cases of immune effector cell–associated neurotoxicity syndrome or tumor lysis syndrome.

Infections were seen in 81.8% of patients treated across both levels. Of these, 31.8% were grade 3 in severity and 9.1% were grade 4 (life-threatening). Opportunistic infections were experienced by 50% of patients, of which only one patient had a grade 3 or higher opportunistic infection. The most commonly reported events were CMV infection or reinfection (27% for both) or COVID-19 and oral candidiasis (18% for each).

Odronextamab Regulatory History and Further Study

In August of 2025, the U.S. Food and Drug Adminsitration (FDA) issued a complete response letter (CRL) for a biologics license application for odronextamab for the treatment of relapsed/refractory follicular lymphoma following two or more lines of systemic therapy.Additionally, in March of 2024, the agent received two CRLs for DLBCL and follicular lymphoma. In both cases, the applications were based on phase 2 findings. The CRL issued in August noted concerns with site inspections completed at a plant ran by Catalent Indiana LLC.

Odronextamab is the subject of several clinical trials across several disease settings, either as monotherapy or in various combination regimens, including the phase 3 OLYMPIA-2 study for follicular lymphoma and the phase 3 OLYMPIA-5 study looking at odronextamab plus lenalidomide for follicular lymphoma.

“Odronextamab plus chemotherapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): First Results from part 1 of the Phase 3 Olympia-3 study,” by Dr. Jean-Marie Michot et al., 

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Odronextamab, a CD20 and CD3 bispecific antibody, shows promising early efficacy in combination with CHOP chemotherapy for untreated diffuse large B-cell lymphoma (DLBCL). In the OLYMPIA-3 study, the 160 mg dose achieved a 100% objective and complete response rate, leading to its selection for further study. Safety profiles were manageable, with no new safety signals. Common side effects included neutropenia and cytokine release syndrome. Despite previous regulatory setbacks, odronextamab continues to be investigated in various clinical trials for lymphoma treatment.

Odronextamab Plus CHOP Shows Early Efficacy in DLBCL

Consolidation tiragolumab plus Tecentriq does not improve progression-free survival in advanced lung cancer compared to Imfinzi.

Among patients locally advanced, unresectable, stage 3 non-small cell long cancer (NSCLC) that has not progressed after platinum-based concurrent chemoradiation (cCRT), consolidation therapy with tiragolumab plus Tecentriq (atezolizumab) did not improve independent review facility (IRF)-assessed progression-free survival (PFS) versus standard Imfinzi (durvalumab) therapy, study results have shown.

Findings from the phase 3 SKYSCRAPER-03 trial were presented at the 2025 ESMO Congress.

At a median follow-up of 30.7 months, the median IRF-PFS in the overall population was 14.2 months in patients receiving the combination versus 13.8 months in patients treated with Imfinzi. The 24-month PFS event-free rates were 39% and 38.5%, respectively. The median overall survival (OS) was 45.6 months versus 45.8 months, respectively. The 24-month OS event-free rates were 67% versus 66.3%, respectively.

Independent review facility (IRF)-assessed progression-free survival (PFS): the length of time a patient lives without their cancer growing or spreading, as determined by a group of expert doctors who review the scans independently from the study doctors.

Overall survival (OS): the percentage of people in a study who are still alive after a certain period of time.

ECOG performance status: a scale that doctors use to describe a patient's general well-being and how capable they are of performing ordinary daily tasks.

The primary end point was also missed in PD-L1–positive patients with a median IRF-PFS of 19.4 months versus 16.6 months in patients treated with the combination versus Imfinzi, respectively. The median OS in these patients was not estimable versus 54.8 months, respectively. The 24-month PFS and OS event-free survival rates were 46.1% versus 42.9% and 72.2% versus 69.2%, respectively.

“SKYSCRAPER-03 did not meet its primary end point of IRF-PFS. There were no new or unexpected [safety] findings,” said first study author Dr. Rafal Dziadziuszko, department of oncology and radiotherapy of the Medical University of Gdansk, Poland.

What Was the Safety Profile of the Combination and Monotherapy Arms in the Trial?

“Tiragolumab plus [Tecentriq] demonstrated a tolerable safety profile, consistent with previous observations for the combination,” said Dziadziuszko.

Grade 3 (severe)/4 (life-threatening) treatment-related side effects occurred in 13.8% of patients in the combination arm, with serious treatment-related side effects experienced by 11.5%. There were two patient deaths considered to be related to the combination treatment. In the Imfinzi arm, grade 3/4 treatment-related side effects and serious treatment-related side effects each occurred in 10.7% of patients. There were seven patient deaths considered to be related to Imfinzi treatment.

What Was the Study Rationale and Design for the Trial?

Regarding the rationale for the study, Dziadziuszko explained, “Consolidation [Imfinzi] is the standard of care for patients with unresectable, stage 3 NSCLC that has not progressed following cCRT; however, disease recurrence [still] represents an unmet need.”

He added that the immune checkpoint target TIGIT has a role in cancer immune evasion and the study hypothesis was that tiragolumab, an anti-TIGIT monoclonal antibody, could potentially augment antitumor activity when used in combination with immunotherapies such as Tecentriq.

The open-label phase 3 trial was launched to test this hypothesis in patients with newly diagnosed, unresectable, stage 3 NSCLC whose disease has not progressed following at least two cycles of definitive platinum-based cCRT. Patients had to have known PD-L1 status and an ECOG performance status of 0 or 1. Patients with EGFR- or ALK-positive tumors were not eligible for enrollment.

At 1 to 42 days post cCRT, patients were randomized to combination therapy with tiragolumab (840 mg IV every four weeks) plus Tecentriq (1680 mg IV every four weeks) or single-agent Imfinzi (10 mg/kg IV every two weeks or 1500 mg IV every four weeks). Patient could receive up to 13 cycles of treatment (28-day cycles).

What Were the Patient Characteristics in the Trial?

Patient characteristics were well balanced between the two study arms. The median age was 64 years in the combination arm versus 65 years in the Imfinzi arm. About half of patients in each arm were aged less than 65 years at 50.8% and 47.4%, respectively. About 80% of patients in each arm were male, about 60% were White and about 35% were Asian. Patients’ ECOG performance status was mostly split evenly between 0 and 1, with a slightly higher number of patients in each arm at ECOG 1 status. About 75% of patients in each arm were former tobacco users and about 20% were current tobacco users.

“SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT),” Dr. Rafal Dziadziuszko et al, presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA69.

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Consolidation therapy with tiragolumab plus Tecentriq did not improve progression-free survival (PFS) compared to standard Imfinzi therapy in patients with locally advanced, unresectable stage 3 non-small cell lung cancer (NSCLC) post-platinum-based concurrent chemoradiation. The phase 3 SKYSCRAPER-03 trial showed similar median PFS and overall survival (OS) between the two groups. The safety profile of the combination therapy was consistent with previous observations, with slightly higher rates of severe side effects compared to Imfinzi. The study aimed to address disease recurrence by targeting the TIGIT immune checkpoint.

Tiragolumab Plus Tecentriq Doesn’t Improve NSCLC Outcomes

Sac-TMT improved progression-free survival in patients with HR+/HER2– breast cancer.

Patients with previously treated, locally advanced or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer experienced superior progression-free survival when treated with the TROP2-targeted antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT; SKB264; MK-2870) compared with chemotherapy, clinical trial results have shown.

Updated findings from the phase 3 OptiTROP-Breast02 trial were presented at the 2025 ESMO Congress in Berlin.

Notably, sac-TMT elicited a 65% reduction in the risk of disease progression or death versus chemotherapy and showed a consistent benefit across subgroups. At a median follow-up of 7.4 months, the median PFS (mPFS) in patients receiving sac-TMT (8.3 months) was approximately twice that of patients receiving chemotherapy (4.1 months).

Progression-free survival (PFS): the length of time a person lives with cancer without the cancer getting worse.

Objective response rate (ORR): the percentage of patients in a study whose cancer shrinks or disappears after treatment.

Disease control rate (DCR): the percentage of patients in a study whose cancer either shrinks, disappears, or remains stable with treatment.

Duration of response (DOR): the length of time a patient continues to have a response to a treatment without the cancer progressing.

Anemia: a condition where your body does not have enough healthy red blood cells to carry adequate oxygen to your tissues, often leading to fatigue.

Neutropenia: a condition in which a person has a low number of neutrophils, which are a specific type of white blood cell important for fighting infection.

Stomatitis: a general term for inflammation or soreness inside the mouth, which can include mouth sores.

Additionally, an interim analysis of overall survival (OS) revealed a positive trend among those receiving sac-TMT compared to those receiving chemotherapy.

“The current chemotherapy options [for HR-positive/HER2-negative breast cancer] show limited efficacy,” said Man Li, professor at the Second Affiliated Hospital of Dalian Medical University, during the presentation. “Sac-TMT has shown promising activity in pretreated patients with HR-positive/HER2-negative metastatic breast cancer in [a] phase 2 study.”

These new statistically significant and clinically meaningful efficacy data from OptiTROP-Breast02, along with an observed manageable safety profile, strengthen the case for sac-TMT as a potential new treatment option for this patient population who comprise a vast majority of global breast cancer cases.

“The OptiTROP-Breast02 study supports sac-TMT as a new treatment option for patients with HR+/HER2– breast cancer following endocrine-based therapy and chemotherapy,” said Li.

OptiTROP-Breast02 is a global randomized open-label study evaluating the efficacy and safety of sac-TMT versus investigator’s choice of chemotherapy (ICC) in adult patients with unresectable, locally advanced or metastatic HR-positive/HER2-negative breast cancer who had failed at least one line of systemic chemotherapy. The study is assessing the primary end point of PFS, along with secondary end points of investigator-assessed OS, objective response rate, disease control rate and duration of response.

Patients were eligible for participation if they had HR-positive/HER2-negative breast cancer, had between one and four lines of chemotherapy, and had at least one endocrine therapy, CDK 4/6 inhibitor and taxane in any setting. Of 399 patients randomized to either the investigational arm (200 patients) or control arm (199 patients), 200 received 5 mg/kg of intravenous sac-TMT every 2 weeks, while 196 received ICC including eribulin, capecitabine, gemcitabine and vinorelbine.

What Were the Patient Characteristics in the OptiTROP-Breast02 Trial?

Patient characteristics were well balanced between the study arms. Across both arms, the median age was 54 years, two-thirds had an ECOG performance status of 1, about 53% were HER2 zero and 47% were HER2 low. About 96% of patients had visceral metastases and over three-fourths had liver metastases. About three-fourths of patients had received neoadjuvant chemotherapy and all patients had received prior taxane, endocrine therapy and a CDK 4/6 inhibitor. About 56% of patients had received at least two lines of chemotherapy in the advanced/metastatic setting and a little over one-fourth of patients had primary endocrine resistance.

This most recent report of safety data revealed a manageable safety profile, with no new safety signals. In terms of treatment-related side effects, the incidence of all-grade and at least grade 3 (severe) treatment-related side effects was comparable between investigational and control arms. The most common treatment-related side effects for both sac-TMT and chemotherapy were hematologic toxicities, including decreased white blood cell count, anemia and neutropenia. While stomatitis was more frequent in patients receiving sac-TMT (63% versus 8%), Li noted that these side effects were primarily low-grade and manageable.

Treatment discontinuation occurred in 87 and 138 patients in the investigational and control arms, respectively. The most common reason for discontinuation was radiographic disease progression in both the investigational arm (80 patients) and control arm (122 patients).

Regarding next steps Li said, “Phase 3 studies of sac-TMT as a monotherapy and/or in combination with Keytruda (pembrolizumab) in patients with chemotherapy-naïve HR-positive/HER2-negative breast cancer are ongoing globally and in China.”

“Sacituzumab tirumotecan (sac-TMT) vs investigator's choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): results from the randomized, multi-center phase 3 OptiTROP-Breast02 study” by Man Li, presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin Germany. Abstract LBA23.

Sacituzumab tirumotecan (sac-TMT) demonstrated superior progression-free survival (PFS) compared to chemotherapy in patients with previously treated, locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer, according to the OptiTROP-Breast02 trial. Sac-TMT reduced the risk of disease progression or death by 65% and showed a positive trend in overall survival. The trial confirmed sac-TMT's manageable safety profile, with hematologic toxicities being the most common side effects. Ongoing phase 3 studies are evaluating sac-TMT as monotherapy and in combination with pembrolizumab.

Jason M Broderick

Jaypirca Matches Imbruvica's Effectiveness for CLL, With Hints of Long-Term Benefit

Odronextamab Plus CHOP Shows Early Efficacy in DLBCL

Tiragolumab Plus Tecentriq Doesn’t Improve NSCLC Outcomes

HR+/HER2- Metastatic Breast Cancer Progression Improved With Sac-TMT

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