Sasanlimab

Pfizer has terminated a Phase I clinical trial evaluating PF-08046037 (also known as SGN-PDL1iT), an immunostimulatory antibody conjugate targeting PD-L1, as monotherapy and in combination with the anti-PD-1 antibody sasanlimab in patients with advanced solid tumors. The NCT06974734 clinical trial terminated after enrolling only eight participants across multiple planned cohorts, according to a ClinicalTrials.gov registry update verified in April 2026. No reason for the termination was disclosed. The open-label, non-randomized Phase I study enrolled adults with advanced or metastatic non-small cell lung cancer, head and neck squamous cell carcinoma, melanoma, or pancreatic ductal adenocarcinoma. The trial followed a sequential design moving through dose escalation, optimization, and expansion phases for both monotherapy and combination arms. Primary endpoints centered on safety — specifically dose-limiting toxicities within the first 21 days and adverse event incidence over the treatment period — with secondary objectives including pharmacokinetic characterization and preliminary efficacy signals such as objective response rate, duration of response, and progression-free survival assessed by RECIST v1.1. According to the ClinicalTrials.gov posting for the trial, the study was terminated “for strategic business reasons” with no safety and/or efficacy concerns cited. There has so far been no further public explanation from Pfizer for the termination. The trial ended within approximately ten months of its May 2026 start date. PF-08046037 entered clinical testing as part of Pfizer’s inherited Seagen pipeline following the company’s USD 43 billion acquisition of Seagen in 2023. The molecule’s alternate name, SGN-PDL1iT, reflects its Seagen origins. The molecule is an immune-stimulating antibody conjugate (ISAC) targeting PD-L1, designed to deliver a TLR7 agonist payload selectively to tumor-associated antigen-presenting cells. Following PD-L1 binding and internalization, the conjugate activates innate immune signaling within endosomes, promoting antigen presentation and reprogramming the tumor microenvironment toward an anti-tumor response. Preclinical studies showed targeted immune activation, reduction of suppressive macrophages, and anti-tumor activity with evidence of immune memory, supporting its rationale prior to program termination. The trial assessed PF-08046037 as monotherapy or in combination with sasanlimab, Pfizer’s subcutaneous anti-PD-1 monoclonal antibody developed under the code PF-06801591. Sasanlimab has its own separate clinical trajectory and recently demonstrated efficacy in a Phase III bladder cancer trial, establishing it as a viable standalone asset. Its pairing with PF-08046037 in this study represented an exploratory combination hypothesis — that innate immune activation via the conjugate might synergize with checkpoint blockade. The termination of NCT06974734 fits a broader pattern within Pfizer’s post-acquisition oncology pipeline. The company has discontinued several early-stage Seagen-derived programs since 2023, including assets in the ADC space where early safety or translational data did not meet internal thresholds. Pfizer is simultaneously executing a cost-reduction program targeting approximately USD 7.2 billion in net savings through 2027, with active rationalization of its research portfolio. Under that framework, early-stage programs without compelling early signals face a higher bar for continuation. The ISAC modality itself remains largely unproven in the clinic. The concept of using a tumor-targeting antibody to deliver a TLR agonist payload selectively to the tumor microenvironment is mechanistically appealing — it aims to convert immunologically cold tumors into inflamed ones without the systemic toxicity associated with systemic TLR agonist administration — but the approach carries inherent risks. Systemic immune activation, cytokine release, and off-tumor payload delivery are recognized liabilities, and the eligibility criteria for this trial reflected awareness of those risks through the exclusion of patients with prior immune-mediated toxicities of grade 3 or higher, active autoimmune disease, or significant pulmonary or neurodegenerative conditions. Pfizer has not indicated whether it intends to out-license PF-08046037 or pursue alternative development pathways for the asset. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

The EMA said Friday that Pfizer recently withdrew an application seeking approval of its subcutaneous PD-1 inhibitor sasanlimab for the treatment of Bacillus Calmette-Guérin (BCG)-naive, high-risk, non-muscle invasive bladder cancer (NMIBC). The move came midway through the review process, although the regulator noted that its provisional opinion was that the therapy — to be marketed as Zumrad — could not have been authorised based on current data.Pfizer's submission was based on findings from the Phase III CREST study, in which sasanlimab demonstrated a 32% reduction in the risk of disease-related events when combined with BCG induction plus maintenance therapy versus BCG alone. However, an analysis of overall survival at the time showed no difference between treatment groups after a median follow-up of nearly 41 months.The EMA said that following an initial assessment of the evidence it had submitted a number of questions to Pfizer, and was in the process of reviewing the company's responses at the time the application was withdrawn on February 13.Questions over supporting studyAccording to the agency, its concerns around the submission related to the main findings of the CREST study following "major changes" that were made while the trial was ongoing, including to the statistical method used to determine how effective sasanlimab was, which increased the chance of concluding that the medicine had a beneficial effect.The EMA also questioned whether the study’s main measure of effectiveness — event-free survival (EFS) — was appropriate, as it was assessed by the researchers themselves. The regulator noted that as both the researchers and participants knew which treatment was being given, this could have influenced the assessment. In addition, the agency said it was unclear whether the effect seen with sasanlimab provides a meaningful benefit to patients, particularly as other measures, such as how long patients lived, did not support the EFS findings. The EMA added that giving BCG with Pfizer's therapy also resulted in more side effects, including those affecting the immune system, as well as more interruptions and discontinuations of BCG treatment.In a letter notifying the EMA of its move, Pfizer said the withdrawal of the filing will "allow for additional data collection and analyses to address…questions raised by the Committee for Medicinal Products for Human Use (CHMP)."