A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTITUMOR ACTIVITY OF PF-08052667 AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 18 YEARS OF AGE AND OLDER WITH BLADDER CANCER

Overview

Sasanlimab (PF-06801591; RN-888; WHO 11161) is a humanized IgG4 monoclonal antibody targeting programmed death-1 (PD‑1). It is being developed as a subcutaneous (SC) checkpoint inhibitor dosed most commonly at 300 mg every 4 weeks. Preclinical work showed selective, high-affinity PD‑1 binding, blockade of PD‑L1/PD‑L2, and T‑cell activation without detectable Fc‑mediated effector function. Clinical development includes a pivotal phase 3 trial in BCG‑naïve, high‑risk non–muscle invasive bladder cancer (NMIBC) and early‑phase studies across solid tumors. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

• Binds PD‑1 on activated immune cells and blocks PD‑L1/PD‑L2 interactions, relieving inhibitory signaling and enhancing antitumor T‑cell responses; engineered as IgG4 with minimal Fc effector function. (pubmed.ncbi.nlm.nih.gov)
• Translational analyses from a first‑in‑human study found that higher baseline tumor mutational burden (TMB), PD‑L1, CD8, and interferon‑γ–related signatures were associated with better tumor shrinkage on sasanlimab across tumor types and IV/SC routes. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Non–muscle invasive bladder cancer (BCG‑naïve, high‑risk; Phase 3 CREST, NCT04165317) - Randomized 1:1:1: sasanlimab+BCG induction+maintenance (Arm A; n=352) vs sasanlimab+BCG induction only (Arm B; n=352) vs BCG induction+maintenance (Arm C; n=351). Primary endpoint met: event‑free survival (EFS) improved for Arm A vs Arm C (HR 0.68; 95% CI 0.49–0.94; one‑sided p=0.0095). Estimated 36‑month EFS: 82.1% (Arm A) vs 74.8% (Arm C). Benefit was consistent in CIS and T1 subgroups. (pubmed.ncbi.nlm.nih.gov)
- Key secondary comparison (Arm B vs Arm C) was negative (HR 1.16; p=0.312), underscoring the role of BCG maintenance in the combination. In patients with CIS at randomization, complete response (CR) at any time was 89.8% with sasanlimab+BCG induction+maintenance vs 85.2% with BCG alone; 36‑month CR maintenance among responders was 91.7% vs 67.7%, respectively. Median OS not different at interim analysis (~41‑month follow‑up); study ongoing. (pfizer.com)

Advanced solid tumors (Phase Ib/II; SC 300 mg Q4W) - Dose‑expansion cohorts showed confirmed objective response rates (ORR): 16.4% in NSCLC (n=68) and 18.4% in urothelial carcinoma (n=38). Median PFS was 3.7 months (NSCLC) and 2.9 months (urothelial); median OS 14.7 and 10.9 months, respectively. Responses and survival tended to be higher with elevated PD‑L1 and high TMB. (pmc.ncbi.nlm.nih.gov)

Alternative SC dosing (Phase Ib/II) - A randomized pharmacokinetic study in advanced NSCLC/other malignancies evaluated 300 mg Q4W vs 600 mg Q6W SC dosing; it characterized exposure targets and supported SC schedules for further study. (pmc.ncbi.nlm.nih.gov)

Safety

• In phase Ib/II expansion (SC 300 mg Q4W), grade ≥3 treatment‑related adverse events (TRAEs) occurred in 13.2% of patients; overall tolerability was described as favorable. (pmc.ncbi.nlm.nih.gov)
• In the phase 3 CREST trial, the safety profile of sasanlimab+BCG was reported as consistent with known PD‑1 inhibitor class effects; no new safety signals were highlighted in topline disclosures. (reuters.com)

Further reading

• Preclinical characterization of sasanlimab (mechanism/engineering): Al‑Khami et al., Mol Cancer Ther 2020. (aacrjournals.org)
• Biomarker analyses across tumor types and routes (first‑in‑human): Salgado et al., 2021. (pubmed.ncbi.nlm.nih.gov)
• Phase Ib/II SC sasanlimab in NSCLC and urothelial carcinoma (efficacy/safety): Cho et al., ESMO Open 2023. (pmc.ncbi.nlm.nih.gov)
• Alternative SC dosing PK/safety: Penkov et al., Ther Adv Med Oncol 2024 (open access). (pmc.ncbi.nlm.nih.gov)
• Phase 3 CREST primary results in BCG‑naïve, high‑risk NMIBC: PubMed record and company summary. (pubmed.ncbi.nlm.nih.gov)
• Company development page (mechanism, administration, development status, updated Aug 5, 2025). (pfizeroncologydevelopment.com)

Last updated: Oct 2025

Overview

PF-02921367 is Pfizer’s internal code for dodecyl maltoside (DDM), a nonionic alkylsaccharide surfactant widely used as a mucosal permeability enhancer and formulation excipient. It is being explored intravesically in bladder cancer to transiently increase urothelial permeability and improve delivery of intravesical biologics/oncolytic viruses; it has also been used clinically as an intranasal absorption enhancer in approved and investigational formulations. DDM itself is not an antitumor agent; it functions as a delivery enhancer. (smartpatients.com)

Mechanism of action

• Surfactant/permeation enhancer: DDM transiently perturbs epithelial membranes and tight junctions to increase paracellular and transcellular transport. These effects are rapid and reversible on mucosa. (pubmed.ncbi.nlm.nih.gov)
• In the bladder, DDM has been shown preclinically to enable high-level adenoviral transduction of the urothelium after brief pretreatment or co‑formulation, supporting its use with intravesical viral or gene therapies. (pubmed.ncbi.nlm.nih.gov)

Clinical development status

• Bladder cancer (intravesical, delivery enhancer):
  • Listed as a study treatment alongside the investigational intravesical agent PF‑08052667 (with or without BCG and/or sasanlimab) in a Phase 1 trial for high‑risk non–muscle‑invasive bladder cancer (NCT07206225; record last updated October 23, 2025). (smartpatients.com)
  • Used with the oncolytic adenovirus cretostimogene grenadenorepvec in an expanded access protocol for BCG‑unresponsive NMIBC (NCT06443944). (ichgcp.net)

• Intranasal delivery (absorption enhancer/excipient):
  DDM has been employed clinically to enhance systemic absorption of intranasal drugs (e.g., naltrexone) and is included in FDA‑approved intranasal products (e.g., sumatriptan [Tosymra], diazepam [Valtoco]) as an absorption enhancer excipient. (pubmed.ncbi.nlm.nih.gov)

Efficacy

DDM is not intended to provide direct therapeutic efficacy; rather, it enhances delivery of co‑administered agents.

• Bladder cancer: There are no published human efficacy outcomes attributable to DDM alone in bladder cancer. Preclinical studies showed that 0.1% DDM pretreatment or co‑formulation produced >90% urothelial transduction with adenoviral vectors in rodents, supporting its role to potentiate intravesical gene/oncolytic therapies. (pubmed.ncbi.nlm.nih.gov)

• Intranasal pharmacokinetics (as an example of delivery enhancement in humans): In a volunteer study, adding 0.25% DDM to intranasal naltrexone (~4 mg) increased Cmax ~3‑fold and shortened Tmax from 0.5 h to 0.17 h versus the same dose without DDM. (pubmed.ncbi.nlm.nih.gov)

Safety

• General/mucosal safety: Reviews of alkylsaccharides report that DDM is generally non‑irritating to nasal mucosa at concentrations used clinically and acts via reversible modulation of epithelial permeability. (pubmed.ncbi.nlm.nih.gov)
• Intranasal clinical experience: In trials of intranasal drugs formulated with DDM, local adverse events are typically mild (e.g., application‑site discomfort), with rates on the order of a few percent in randomized studies (example: sumatriptan 10 mg with 0.20% DDM). (pmc.ncbi.nlm.nih.gov)
• Intravesical use: Human safety data specific to intravesical DDM remain limited in the public domain as of October 2025; ongoing studies use DDM as a delivery adjunct, and historical adenoviral bladder gene‑therapy studies support the concept of surfactant‑facilitated transduction, but definitive clinical safety datasets for intravesical DDM itself have not been published. (ichgcp.net)

Further reading

• Identification of DDM as a bladder transduction enhancer (preclinical). (pubmed.ncbi.nlm.nih.gov)
• NCI Drug Dictionary entry for dodecyl maltoside (mechanism in bladder as a surfactant to enhance adenoviral delivery). (cancer.gov)
• Review of intranasal alkylsaccharides (mechanism, clinical use, safety). (pubmed.ncbi.nlm.nih.gov)
• Human PK study: intranasal naltrexone with and without DDM. (pubmed.ncbi.nlm.nih.gov)
• Trial listings where DDM is used as a delivery enhancer with intravesical agents (NCT07206225, NCT06443944). (smartpatients.com)

Note: No standalone human therapeutic efficacy trials of PF‑02921367 (dodecyl maltoside) were found; current clinical use is as a permeation enhancer to support delivery of other active agents. (smartpatients.com)

Last updated: Nov 2025

Overview

PF-08052667 (also listed as SGN-B6N in some pipelines) is an investigational intravesical therapy being studied for non–muscle-invasive bladder cancer (NMIBC). A Phase 1, open‑label, multicenter trial (NCT07206225) began on October 20, 2025, to evaluate PF‑08052667 as monotherapy and in combination with bacillus Calmette–Guérin (BCG) and/or the anti‑PD‑1 antibody sasanlimab. Administration is by intravesical instillation. As of November 2025, no human efficacy or safety outcomes have been reported publicly. [Trial overview, design, and administration details are available from study listings.] (cancer.gov)

Mechanism of action

The sponsor has not publicly specified the molecular target or detailed mechanism of PF‑08052667 as of November 2025. It is distinct from Seagen/Pfizer’s intravenous integrin β6–directed ADC sigvotatug vedotin (SGN‑B6A; PF‑08046047), which targets ITGB6 and delivers the MMAE payload via a protease‑cleavable linker. That related ADC’s preclinical rationale and Phase 1 program are documented separately and should not be conflated with PF‑08052667. (pfizeroncologydevelopment.com)

Efficacy

• No human efficacy data for PF‑08052667 have been posted or published as of November 2025. The ongoing Phase 1 study’s objectives include characterizing antitumor activity during dose optimization/expansion. (cancer.gov)

Safety

• No human safety results for PF‑08052667 have been posted or published as of November 2025. The Phase 1 study’s primary outcomes include dose‑limiting toxicities in the dose‑escalation cohorts. (bcan.org)

Further reading

• A Study to Learn About the Study Medicine PF‑08052667 in People With Bladder Cancer (NCT07206225) – NCI listing: https://www.cancer.gov/clinicaltrials/NCI-2025-07432 (cancer.gov)
• Pfizer trial listing (NCT07206225): https://www.pfizerclinicaltrials.com/find-a-trial/nct07206225-non-muscle-invasive-bladder-cancer-trial (pfizerclinicaltrials.com)
• Bladder Cancer Advocacy Network summary of NCT07206225: https://bcan.org/clinicaltrials/a-study-to-learn-about-the-study-medicine-pf-08052667-in-people-with-bladder-cancer/ (bcan.org)
• Pipeline aggregation noting alias “SGN‑B6N” for PF‑08052667: https://synapse.patsnap.com/drug/7a28bce75f914b73a0f17f0dc212b683 (synapse.patsnap.com)
• Context on Seagen/Pfizer’s integrin β6–directed ADC (separate program):
• Molecular Cancer Therapeutics (preclinical characterization of SGN‑B6A/sigvotatug vedotin): https://pubmed.ncbi.nlm.nih.gov/37619980/ (pubmed.ncbi.nlm.nih.gov)
• Pfizer Oncology Development page for sigvotatug vedotin: https://www.pfizeroncologydevelopment.com/clinical_trial/NCT04389632/molecule/776 (pfizeroncologydevelopment.com)

Notes: - The PF‑08052667 program is in early clinical testing; details such as molecular target, drug class, and pharmacology have not been disclosed on public trial pages as of the dates cited above. - The sigvotatug vedotin (SGN‑B6A) materials are provided only to contextualize a separate, integrin β6–directed ADC program from the same corporate portfolio.

Last updated: Nov 2025

INCLUSION CRITERIA:

1. 18 years of age or older (or the minimum age of consent per local regulations)

2. Histological diagnosis of high-risk, non-muscle invasive urothelial carcinoma of the bladder defined according to the WHO grading system as carcinoma in situ (CIS), with or without concurrent T1/Ta papillary disease. Note: High-grade T1/Ta papillary disease, in the absence of CIS, may be eligible for certain cohorts in Part 2 and 3

3. BCG unresponsive and BCG-exposed cohorts should have persistent or recurrent disease after receiving at least 5 out of 6 doses of the BCG induction therapy.

4. Have refused or are ineligible or not appropriate for radical cystectomy

5. Tissue Requirement: Available tumor tissue within the last 6 months. On-treatment tumor biopsy is optional, unless mandated based on emerging data, or participating in the Biomarker Cohort, or for disease assessment

6. ECOG PS 0 or 1

EXCLUSION CRITERIA:

1. Concomitant anti-cancer therapy for Non-Muscle Invasive Bladder Cancer (NMIBC); and prior radiation therapy to the bladder are not allowed

2. Renal or hepatic impairment; and hematologic abnormalities as defined in the protocol

3. Participants with active, uncontrolled infection as specified in the protocol