On September 8, 2025 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported new paradigm changing findings from the Phase 2 QUILT-3.055 study, demonstrating ANKTIVA (nogapendekin alfa inbakicept-pmln) reverses lymphopenia (low natural killer and T cells) in patients with checkpoint inhibitor-resistant advanced non-small cell lung cancer (NSCLC), with this reversal resulting in significant prolonged median overall survival (mOS) (Press release, ImmunityBio, SEP 8, 2025, View Source [SID1234655829]). The results were presented (P1.11.78) on Sunday, September 7, at the IASLC 2025 World Conference on Lung Cancer in Barcelona, Spain. A video presentation of the data is available on X.com @DrPatSoonShiong.

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Severe lymphopenia (loss of cancer-killing natural killer cells and T cells), is defined by the absolute lymphocyte count (ALC) of less than 1,000 lymphocyte cells/µL. This lowered ALC count is caused by the side effects resulting from current standards of treatment with radiotherapy, chemotherapy and immunotherapy, and is associated with reduced survival across all tumor types.1,2 Although reduced ALC is a recognized risk factor in a many cancers, it has largely been overlooked because no therapies have been approved to address lymphopenia. ANKTIVA is the first therapy under investigation specifically for this purpose.

"These results present the clinical evidence that a low lymphocyte count, as measured by ALC levels, is an actionable, accessible biomarker to identify and treat therapy-induced lymphopenia in cancer patients with ANKTIVA and prolong overall survival," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "ANKTIVA is the first FDA-approved immunotherapy to stimulate natural killer cells, CD4+ CD8+ T cells and memory T cells, the very cells that are depleted resulting in lymphopenia, and that play a key role in the immune system’s fight against cancer. It is my belief that treating lymphopenia in patients with low NK and T cell count, is as essential as the well-established treatment of anemia (low red blood cells count) or of neutropenia (low neutrophil count), which occur as a consequence of chemotherapy, independent of tumor types. By taking this approach, we hope to herald in the paradigm change of treating the immune system itself and thereby allow the immune system to cure the cancer, regardless of its anatomical location. The long-term survival demonstrated in patients with bladder cancer and now in lung cancer provide evidence of the potential validity of this hypothesis, with ANKTVIA as the foundation of the BioShield platform."

Specific findings from the Phase 2 QUILT-3.055 study include:

Participants with a baseline ALC≥1,200 cells/µL and a group mean ALC≥1500 cells/µL at each on-treatment time point (N=44) had greater prolonged OS (21.1 months, 95% CI: 13.9. 42.1)
mOS for study participants with NSCLC, including patients in second line (51%) and third line-plus treatment (49%), was 14.3 months (95% CI 11.7, 17.4), with 23 of 86 participants alive at data cutoff (December 2024)
Among patients treated with ANKTIVA, 80% (69 of 86) exceeded an ALC of 1,200 cells/µL, with mOS of 15.8 months (95% CI 12.6, 21.9) compared to participants who failed to achieve ALC>1,200 cells/µL with mOS of 11.5 months (95% CI 4.2, 13.3); p=0.0057
60% of participants (25/42) treated with ANKTIVA reversed their lymphopenia during at least one on-treatment timepoint.
The randomized Phase 3 ResQ201A trial (NCT06745908) is evaluating ANKTIVA + tislelizumab, a checkpoint inhibitor, versus docetaxel alone in second-line NSCLC patients who have progressed after all standard therapies, including checkpoint inhibitors. Patients interested in enrolling can inquire at org.
The Phase 2 QUILT-3.055 study (NCT03228667) enrolled participants with advanced NSCLC who had developed resistance to checkpoint inhibitor immunotherapy (CPI). Participants continued treatment with the same CPI on which they had progressed, combined with ANKTIVA, to test the hypothesis that AKNTIVA could improve overall survival by reversing lymphopenia and maintaining median ALC≥1,200 cells/µL. The primary endpoint was the change in ALC, including absolute cell count and percentage change from baseline, with ANKTIVA plus CPI during the study and its relationship to mOS. Statistical differences between OS among participants who failed to reverse lymphopenia (ALC<1,200 cells/µL) during treatment vs. those who had a baseline ALC≥1200 cells/µL and maintained a group mean ALC≥1,500 cells/µL while on treatment were compared. The study also assessed the proportion of participants with lymphopenia reversal (baseline ALC<1,200 cells/µL and at least one on-treatment ALC≥1,200 cells/µL).

ANKTIVA is currently approved by the U.S. Food and Drug Administration with Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

About ANKTIVA (nogapendekin alfa inbakicept-pmln)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. A key component in the company’s BioShield platform, ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and driving the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones.

IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE: ANKTIVA is an interleukin-15 (IL-15) receptor agonist indicated with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

WARNINGS AND PRECAUTIONS: Risk of Metastatic Bladder Cancer with Delayed Cystectomy. Delaying cystectomy can lead to the development of muscle-invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after a second induction course of ANKTIVA with BCG, reconsider cystectomy.

DOSAGE AND ADMINISTRATION: For Intravesical Use Only. Do not administer by subcutaneous or intravenous routes.

Please see the complete Indication and Important Safety Information and Prescribing Information for ANKTIVA at Anktiva.com.

On September 8, 2025 I-Mab (NASDAQ: IMAB) (I-Mab or the Company), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, reported accelerated investment in its lead program, givastomig, an investigational Claudin 18.2 (CLDN18.2)-directed bispecific antibody (CLDN18.2 x 4-1BB), including plans to initiate a global randomized Phase 2 study and additional Phase 1b cohorts (Press release, I-Mab Biopharma, SEP 8, 2025, View Source [SID1234655824]). The Company also reiterated its expectations to report Phase 1b dose expansion data in Q1 2026. In addition, I-Mab announced leadership additions, including the appointment of Mr. Wei Fu as Executive Chairman, and the appointment of Dr. Sean Cao as Chief Business Development Officer (CBO).

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"2025 has been a year of significant progress for I-Mab. Compelling Phase 1b combination data and positive investigator engagement have accelerated the givastomig program and reinforced our confidence in its potential to be a best-in-class Claudin 18.2-directed therapy for metastatic gastric cancers in the 1L setting," said Sean Fu, PhD, Chief Executive Officer of I-Mab. "Based on these accomplishments, we are expanding our investment in givastomig, with plans to initiate a randomized Phase 2 study in Q1 2026."

"This is an exciting time for I-Mab, marked by clinical progress and organizational development," said Mr. Wei Fu, Executive Chairman of I-Mab. "I am very excited to work side-by-side with Sean Fu and the executive team as we embark on the next stage of the Company’s growth. With each step forward, I-Mab maintains an unwavering focus on value creation, supported by a strong cash balance and dedication to advancing our mission to improve the lives of patients globally."

Givastomig Clinical Program Overview:

1L Gastric Cancer (GC) Studies:

•
Phase 1b dose expansion data expected in Q1 2026: Phase 1b dose expansion cohorts evaluating givastomig at two dose levels (8mg/kg and 12mg/kg) in combination with nivolumab and chemotherapy (n=40) as a first-line (1L) treatment for patients with metastatic gastric cancers.
•
Initiation of a global randomized Phase 2 study in 1L metastatic gastric cancers: The Company intends to initiate a randomized Phase 2 study in 1L metastatic gastric cancers evaluating givastomig in combination with nivolumab and chemotherapy versus nivolumab and chemotherapy alone. Progression free survival (PFS) data are expected in 2027.
•
Initiation of a 1L metastatic GC cohort for patients who do not qualify for checkpoint inhibitors or the existing approved CLDN18.2 1L GC therapy (Double-Low): The Company intends to initiate an additional Phase 1b cohort evaluating givastomig in combination with chemotherapy (n=20) as a 1L treatment for patients with metastatic gastric cancers whose tumors express Claudin 18.2 in <75% of cells (CLDN-Low) and CPS scores <1 (PD-L1 Low), known as (Double-Low) patients. This population represents a significant unmet medical need since these patients are not

eligible to receive the existing approved CLDN18.2-directed therapy or immunotherapies. The current standard of care is chemotherapy alone in this patient population.
Expansion of Givastomig into Gastrointestinal Malignancies Characterized by CLDN18.2 Expression:

•
1L Pancreatic Ductal Adenocarcinoma (PDAC): The Company intends to initiate an additional Phase 1b cohort in 1L, CLDN18.2-positive PDAC evaluating givastomig in combination with chemotherapy.
•
1L Biliary Tract Cancer (BTC): The Company intends to initiate an additional Phase 1b cohort in 1L, CLDN18.2-positive BTC evaluating givastomig in combination with a checkpoint inhibitor, and chemotherapy.
Investigator Initiated Trials (IITs) Broaden Evaluation into Other Tumor Types in a Neoadjuvant Setting:

•
Dr. Kohei Shitara, National Cancer Center Hospital East, Japan: A single arm study evaluating givastomig in combination with a checkpoint inhibitor and chemotherapy as a 1L neoadjuvant therapy for locally advanced, CLDN18.2-positive, resectable gastric cancers.
•
Dr. Jeremy Kratz, University of Wisconsin, sponsored by the Department of Veterans Affairs: A single arm study evaluating givastomig in combination with chemotherapy as a 1L neoadjuvant therapy for CLDN18.2-positive, resectable pancreatic cancer.
Governance and Leadership Updates:

Mr. Wei Fu, the current Chairman of the Board of Directors (the Board) has been appointed to the role of Executive Chairman by the Board. Additionally, the Board has appointed Dr. Sean Cao to the newly created role of Chief Business Development Officer (CBO). Dr. Cao will devote approximately half of his professional time to I-Mab to further support I-Mab’s growth. Dr. Cao joins I-Mab from CBC Group and affiliates, bringing expertise in business development.

About Givastomig

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further exploratory studies in other CLDN18.2-positive gastrointestinal tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.

Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.

On September 8, 2025 Galectin therapeutics presented its corporate presentation (Presentation, Galectin Therapeutics, SEP 8, 2025, View Source [SID1234655822]).

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On September 8, 2025 Eli Lilly and Company (NYSE: LLY) reported positive topline results from the Phase 3 BRUIN CLL-313 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, versus chemoimmunotherapy (bendamustine plus rituximab), in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions (Press release, Eli Lilly, SEP 8, 2025, View Source [SID1234655821]). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemoimmunotherapy, as assessed by an independent review committee (IRC), indicating one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study.

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Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but was trending strongly in favor of pirtobrutinib and will be tested for statistical significance at the time of the primary OS analysis, which is anticipated to occur in 2026. The overall safety profile of pirtobrutinib in BRUIN CLL-313 was generally consistent with previously reported trials across treatment settings.

Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. The results from the BRUIN CLL-313 and BRUIN CLL-314 studies will form the basis for seeking label expansions in earlier lines of therapy, with global regulatory submissions beginning later this year.

"The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the potential of pirtobrutinib to be a meaningful treatment option for people with untreated CLL/SLL," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "With this third positive Phase 3 study, we continue to build the clinical evidence supporting the possible role of pirtobrutinib in a variety of CLL/SLL treatment settings, including treatment-naïve, BTK inhibitor-naïve and BTK inhibitor exposed. We look forward to presenting these data, as well as data from the recently announced positive BRUIN CLL-314 study, at upcoming medical meetings and preparing global regulatory submissions, with the goal of making pirtobrutinib an option for a wider group of patients who might benefit."

These data build on the previously reported positive results from the BRUIN Phase 1/2 trial, the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population, and the Phase 3 BRUIN CLL-314 trial, the first-ever head-to-head Phase 3 trial versus ibrutinib in CLL to include treatment-naïve patients. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov.

About BRUIN CLL-313
BRUIN CLL-313 is a Phase 3, global, randomized, open-label study of pirtobrutinib versus chemoimmunotherapy (bendamustine plus rituximab) in people with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions who have not been previously treated. The trial enrolled 282 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or bendamustine plus rituximab (BR) per labeled doses. BR is a chemoimmunotherapy regimen used in the treatment of CLL. The primary endpoint is progression-free survival (PFS) as assessed by blinded independent review committee (IRC). Secondary endpoints include investigator and IRC assessed overall response rate (ORR), duration of response (DoR), and PFS, overall survival (OS), time to next treatment (TTNT), safety and tolerability and patient-reported outcomes (PRO).

About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.

INDICATIONS FOR JAYPIRCA (pirtobrutinib)
Jaypirca is a kinase inhibitor indicated for the treatment of

Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR JAYPIRCA (pirtobrutinib)

Infections: Fatal and serious infections (including bacterial, viral, fungal) and opportunistic infections occurred in Jaypirca-treated patients. In a clinical trial, Grade ≥3 infections occurred in 24% of patients with hematologic malignancies, most commonly pneumonia (14%); fatal infections occurred (4.4%). Sepsis (6%) and febrile neutropenia (4%) occurred. In patients with CLL/SLL, Grade ≥3 infections occurred (32%), with fatal infections occurring in 8%. Opportunistic infections included Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients at increased risk for infection, including opportunistic infections. Monitor patients for signs and symptoms, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Hemorrhage: Fatal and serious hemorrhage has occurred with Jaypirca. Major hemorrhage (Grade ≥3 bleeding or any central nervous system bleeding) occurred in 3% of patients, including gastrointestinal hemorrhage; fatal hemorrhage occurred (0.3%). Bleeding of any grade, excluding bruising and petechiae, occurred (17%). Major hemorrhage occurred in patients taking Jaypirca with (0.7%) and without (2.3%) antithrombotic agents. Consider risks/benefits of co-administering antithrombotic agents with Jaypirca. Monitor patients for signs of bleeding. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca. Consider benefit/risk of withholding Jaypirca 3-7 days pre- and post-surgery depending on type of surgery and bleeding risk.

Cytopenias: Jaypirca can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. In a clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%), developed in Jaypirca-treated patients. Grade 4 decreased neutrophils (14%) and Grade 4 decreased platelets (6%) developed. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Cardiac Arrhythmias: Cardiac arrhythmias occurred in patients who received Jaypirca. In a clinical trial of patients with hematologic malignancies, atrial fibrillation or flutter were reported in 3.2% of Jaypirca-treated patients, with Grade 3 or 4 atrial fibrillation or flutter in 1.5%. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred (0.5%). Patients with cardiac risk factors such as hypertension or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue Jaypirca.

Second Primary Malignancies: Second primary malignancies, including non-skin carcinomas, developed in 9% of Jaypirca-treated patients. The most frequent malignancy was non-melanoma skin cancer (4.6%). Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor for development of second primary malignancies.

Hepatotoxicity, Including Drug-Induced Liver Injury (DILI): Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, has occurred in patients treated with BTK inhibitors, including Jaypirca. Evaluate bilirubin and transaminases at baseline and throughout Jaypirca treatment. For patients who develop abnormal liver tests after Jaypirca, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold Jaypirca. Upon confirmation of DILI, discontinue Jaypirca.

Embryo-Fetal Toxicity: Jaypirca can cause fetal harm in pregnant women. Administration of pirtobrutinib to pregnant rats caused embryo-fetal toxicity, including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended 200 mg/day dose. Advise pregnant women of potential fetal risk and females of reproductive potential to use effective contraception during treatment and for one week after last dose.

Adverse Reactions (ARs) in Patients Who Received Jaypirca

The most common (≥20%) ARs in the BRUIN pooled safety population of patients with hematologic malignancies (n=593) were decreased neutrophil count (46%), decreased hemoglobin (39%), fatigue (32%), decreased lymphocyte count (31%), musculoskeletal pain (30%), decreased platelet count (29%), diarrhea (24%), COVID-19 (22%), bruising (21%), cough (20%).

Mantle Cell Lymphoma

Serious ARs occurred in 38% of patients. Serious ARs occurring in ≥2% of patients were pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%). Fatal ARs within 28 days of last Jaypirca dose occurred in 7% of patients, most commonly due to infections (4.7%), including COVID-19 (3.1% of all patients).

Dose Modifications and Discontinuations: ARs led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dosage modification in >5% of patients included pneumonia and neutropenia. ARs resulting in permanent discontinuation in >1% of patients included pneumonia.

Most common ARs (≥15%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (29; 1.6), musculoskeletal pain (27; 3.9), diarrhea (19; -), edema (18; 0.8), dyspnea (17; 2.3), pneumonia (16; 14), bruising (16; -).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥10% of Patients: hemoglobin decreased (42; 9), platelet count decreased (39; 14), neutrophil count decreased (36; 16), lymphocyte count decreased (32; 15), creatinine increased (30; 1.6), calcium decreased (19; 1.6), AST increased (17; 1.6), potassium decreased (13; 1.6), sodium decreased (13; -), lipase increased (12; 4.4), alkaline phosphatase increased (11; -), ALT increased (11; 1.6), potassium increased (11; 0.8). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (10), platelets decreased (7), lymphocytes decreased (6).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Serious ARs occurred in 56% of patients. Serious ARs occurring in ≥5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%). Fatal ARs within 28 days of last Jaypirca dose occurred in 11% of patients, most commonly due to infections (10%), including sepsis (5%) and COVID-19 (2.7%).

Dose Modifications and Discontinuations: ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs resulting in dose reductions in >1% included neutropenia; treatment interruptions in >5% of patients included pneumonia, neutropenia, febrile neutropenia, and COVID-19; permanent discontinuation in >1% of patients included second primary malignancy, COVID-19, and sepsis.

Most common ARs (≥20%), excluding laboratory terms (all Grades %; Grade 3-4 %): fatigue (36; 2.7), bruising (36; -), cough (33; -), musculoskeletal pain (32; 0.9), COVID-19 (28; 7), pneumonia (27; 16), diarrhea (26; -), abdominal pain (25; 2.7), dyspnea (22; 2.7), hemorrhage (22; 2.7), edema (21; -), nausea (21; -), pyrexia (20; 2.7), headache (20; 0.9).

Select Laboratory Abnormalities (all Grades %; Grade 3 or 4 %) that Worsened from Baseline in ≥20% of Patients: neutrophil count decreased (63; 45), hemoglobin decreased (48; 19), calcium decreased (40; 2.8), platelet count decreased (30; 15), sodium decreased (30; -), lymphocyte count decreased (23; 8), ALT increased (23; 2.8), AST increased (23; 1.9), creatinine increased (23; -), lipase increased (21; 7), alkaline phosphatase increased (21; -). Grade 4 laboratory abnormalities in >5% of patients included neutrophils decreased (23).

Drug Interactions

Strong CYP3A Inhibitors: Concomitant use with Jaypirca increased pirtobrutinib systemic exposure, which may increase risk of Jaypirca ARs. Avoid use of strong CYP3A inhibitors with Jaypirca. If concomitant use is unavoidable, reduce Jaypirca dosage according to approved labeling.

Strong or Moderate CYP3A Inducers: Concomitant use with Jaypirca decreased pirtobrutinib systemic exposure, which may reduce Jaypirca efficacy. Avoid concomitant use of Jaypirca with strong or moderate CYP3A inducers. If concomitant use with moderate CYP3A inducers is unavoidable, increase Jaypirca dosage according to approved labeling.

Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: Concomitant use with Jaypirca increased their plasma concentrations, which may increase risk of adverse reactions related to these substrates for drugs that are sensitive to minimal concentration changes. Follow recommendations for these sensitive substrates in their approved labeling.

Use in Special Populations

Pregnancy and Lactation: Due to potential for Jaypirca to cause fetal harm, verify pregnancy status in females of reproductive potential prior to starting Jaypirca and advise use of effective contraception during treatment and for one week after last dose. Presence of pirtobrutinib in human milk is unknown. Advise women not to breastfeed while taking Jaypirca and for one week after last dose.

Geriatric Use: In the pooled safety population of patients with hematologic malignancies, patients aged ≥65 years experienced higher rates of Grade ≥3 ARs and serious ARs compared to patients <65 years of age.

Renal Impairment: Severe renal impairment increases pirtobrutinib exposure. Reduce Jaypirca dosage in patients with severe renal impairment according to approved labeling.

PT HCP ISI MCL_CLL AA JUN2024

Please see Prescribing Information and Patient Information for Jaypirca.

On September 8, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Bristol Myers Squibb Company (NYSE: BMY, "BMS") reported interim data from a global randomized Phase 2 trial (NCT06449209) evaluating pumitamig (also known as BNT327 or BMS986545), an investigational bispecific antibody targeting PD-L1 x VEGF-A, plus chemotherapy in patients with extensive-stage small cell lung cancer ("ES-SCLC") (Press release, BioNTech, SEP 8, 2025, View Source [SID1234655818]). The data, which are consistent with data presented at the European Lung Cancer Congress ("ELCC") 2025 from a Phase 2 trial conducted in China (NCT05844150), showed encouraging anti-tumor responses with a positive trend in the secondary endpoint progression free survival. Pumitamig plus chemotherapy demonstrated a manageable safety profile with no new safety signals and a low discontinuation rate. The data are being presented today as a late-breaker oral presentation at the IASLC 2025 World Conference on Lung Cancer ("WCLC") hosted by the International Association for the Study of Lung Cancer in Barcelona.

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"Small cell lung cancer is the most aggressive type of lung cancer with rapid growth, a poor prognosis and 5-year relative survival rate of just 5% in advanced stages.1,2,3 While approximately 60-70% of patients initially respond to current standard of care treatments, most progress within months after treatment signifying an urgent need for new treatment options which improve outcomes," said John V. Heymach, M.D., Lead Investigator and Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "The response rate and early progression free survival we are seeing in this interim analysis are encouraging and merit further investigation in a larger trial to validate pumitamig’s potential to offer patients more durable anti-tumor responses relative to current standard of care."

The interim analysis included 43 patients with untreated extensive-stage small cell lung cancer (Cohort 1) who received pumitamig in combination with standard of care chemotherapy in two dose levels. At the August 7, 2025 data cut-off, among 38 efficacy-evaluable patients, the confirmed overall response rate was 76.3% (85.0% at 20 mg/kg [dose level 1] and 66.7% at 30 mg/kg [dose level 2]) and the disease control rate (DCR) was 100%. The mean best percentage change in tumor size showed a tumor shrinkage of 56.7% with 89.5% of patients achieving early tumor shrinkage. Median progression-free survival (mPFS) was 6.8 months (6.3 months at 20 mg/kg and 7.0 months at 30 mg/kg), with mOS not being mature at the time of the analysis. Pumitamig plus chemotherapy showed a manageable safety profile, with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-(L)1 and anti-VEGF monotherapies, and a discontinuation rate of 14%. Out of 43 patients, pumitamig-related treatment-emergent adverse events of Grade ≥3 were reported in 1 patient at dose level 1 and five patients at dose level 2.

"Every innovation we pursue starts with the needs of patients. These interim data for pumitamig presented today show encouraging signals for our science-driven approach to address two fundamental drivers of small cell lung cancer in one single molecule," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "Our ultimate goal is to translate science into meaningful survival benefits for many patients by overcoming some of the biggest treatment challenges, not only in small cell lung cancer but also across other difficult-to-treat solid tumors. These interim data for pumitamig represent an important step in the right direction."

"Today’s data add to the growing body of evidence indicating the potential of pumitamig to improve outcomes across a wide range of solid tumors," said Bryan Campbell, Senior Vice President, Head of Program Leadership, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb. "These are the first-ever data in a global population in advanced small cell lung cancer for a PD-(L)1 x VEGF bispecific antibody, supporting a possible new standard of care for patients with extensive-stage small cell lung cancer. We look forward to continuing to jointly advance research and development of pumitamig as a potential new treatment option with meaningful clinical benefit for patients in need."

A global randomized Phase 3 trial, ROSETTA-LUNG-01 (NCT06712355), evaluating pumitamig plus chemotherapy versus atezolizumab plus chemotherapy as a first-line treatment in patients with untreated ES-SCLC is ongoing. The pivotal trial is enrolling patients at clinical trial sites in the United States, the United Kingdom, Türkiye, China, the Republic of Korea, and Australia with additional sites planned to open globally. Pumitamig received Orphan Drug designation from the U.S. Food and Drug Administration ("FDA") for the treatment of patients with small cell lung cancer in 2025.

The full abstract is available on the WCLC website. Click here for further information on BioNTech’s pipeline assets.

About the BNT327-01 Phase 2 clinical trial
The global randomized, open-label, parallel group Phase 2 clinical trial (BNT327-01; NCT06449209) evaluated pumitamig (BNT327/BMS986545) in patients with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) who progressed on first- or second-line treatment (Cohort 2 and Cohort 3). In Cohort 1, patients received pumitamig in two dose levels + chemotherapy (etoposide+carboplatin) for four cycles, followed by pumitamig maintenance for up to 2 years or until disease progression or unacceptable toxicity to identify an optimized dose for future clinical investigation. Cohort 2 and Cohort 3 explored the combination of two dose levels of pumitamig plus paclitaxel, or topotecan in the second- or third-line setting. The co-primary endpoints of the trial were per RECIST 1.1 objective response rate (ORR), change in tumor size and early tumor shrinkage, and safety per NCI CTCAE v5.0. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS).

About Small Cell Lung Cancer
Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases, with an estimated 250,000 new cases globally per year.1 It is the most aggressive type of lung cancer often spreading early to other parts of the body and developing resistance mechanisms which makes it more challenging to treat.1,2 Platinum-based chemotherapy combined with etoposide chemotherapy has been the standard first-line treatment for decades. While the addition of immune checkpoint inhibitors to chemotherapy has shown improved survival outcomes for patients with advanced or extensive-stage disease, most patients progress within months after treatment, and the prognosis remains poor. The 5-year survival rate for patients with extensive-stage SCLC is only 5%, emphasizing the need for new treatment options that extend progression-free survival.2, 3

About pumitamig (also known as BNT327 or BMS986545)
Pumitamig is a novel investigational bispecific antibody, jointly developed by BioNTech and BMS, combining two complementary, validated mechanisms in oncology into one single molecule. Pumitamig combines PD-L1 checkpoint inhibition aimed at restoring T cells’ ability to recognize and destroy tumor cells with the neutralization of VEGF-A. The blocking of VEGF-A is aimed at reversing the tumor’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumor cells (anti-angiogenesis effect), with the intention of preventing the tumor from growing and proliferating. Pumitamig may be differentiated via its mechanism of action of targeting PD-L1 on tumor cells to localize anti-VEGF activity within the tumor microenvironment, aiming to enhance therapeutic precision and minimize systemic exposure.

More than 1,200 patients have been treated with pumitamig in clinical trials to date. More than 20 clinical trials are currently ongoing or planned to evaluate pumitamig either as a monotherapy or in combination with other treatment modalities targeting different oncogenic pathways in more than 10 solid tumor indications. Multiple global trials are ongoing or planned to start in 2025, including three global clinical trials with registrational potential evaluating pumitamig plus chemotherapy compared to standard of care treatments in first-line small cell lung cancer (ROSETTA LUNG-01; NCT06712355), first-line non-small cell lung cancer (ROSETTA LUNG-02; NCT06712316) and first-line triple-negative breast cancer (ROSETTA BREAST-01). Additional trials are ongoing exploring novel treatment combinations of pumitamig, including combinations with BioNTech’s proprietary antibody-drug conjugate candidates ("ADCs") or immunomodulator candidates.