“How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question

Pfizer's Sasanlimab Boosts Survival In Bladder Cancer

Pfizer Inc. (NYSE: PFE) today announced positive topline results from its pivotal Phase 3 CREST trial evaluating sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with Bacillus Calmette-Guérin (BCG) as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). The study met its primary endpoint of event-free survival (EFS) by investigator assessment, demonstrating a clinically meaningful and statistically significant improvement with sasanlimab in combination with BCG (induction and maintenance) as compared to BCG alone (induction and maintenance).

"Patients with BCG-naïve high-risk non-muscle invasive bladder cancer have high rates of recurrence and progression," said Neal Shore, M.D., FACS, Medical Director for the Carolina Urologic Research Center, and lead investigator for the CREST trial. "These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naïve, high-risk non-muscle invasive bladder cancer, including patients with carcinoma in-situ (CIS), providing prolonged event-free survival which may delay or reduce the need for more aggressive treatment options. Administered subcutaneously every four weeks, sasanlimab, if approved, could also help lower the treatment burden on both patients and healthcare systems."

Each year, approximately 100,000 people globally are diagnosed with high-risk NMIBC.3 Induction therapy with BCG followed by maintenance has been the standard of care for patients with high-risk NMIBC for decades.4 40-50% of patients experience recurrent disease, often requiring radical cystectomy,5,6,7 which is associated with significant risks8,9,10 and bladder-sparing treatment options are still limited.11,12

"The initial therapy of high-risk, non-muscle invasive bladder cancer with BCG has not advanced in decades. Today's pivotal Phase 3 CREST results are potentially practice-changing, representing the first advance in therapy for BCG-naïve, high-risk, non-muscle invasive cancer in over 30 years," said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. "These results reinforce Pfizer's leadership in genitourinary cancer research and development, demonstrating our ongoing commitment to deliver new treatment options for patients with bladder cancer."

The overall safety profile of sasanlimab in combination with BCG was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab. The profile of sasanlimab was also generally consistent with the reported safety profile of PD-1 inhibitors.

Results will be submitted for presentation at an upcoming medical congress. Pfizer plans to discuss these data with global health authorities to support potential regulatory filings. Sasanlimab also continues to be investigated in combination with Pfizer's antibody drug conjugate (ADC) portfolio in advanced solid tumors.

About CREST

The CREST trial is a Phase 3, multinational, randomized, open-label, three parallel-arm study of sasanlimab, an anti-PD-1 mAb, in combination with BCG (BCG induction with or without BCG maintenance) versus BCG (induction and maintenance) in participants with BCG-naïve, high-risk NMIBC. Patients were randomized to receive sasanlimab 300 mg by subcutaneous (SC) injection every four weeks up to cycle 25 (cycle = four weeks), in combination with BCG once weekly for six consecutive weeks (induction period) followed (Arm A) or not (Arm B) by maintenance with BCG, or BCG induction and maintenance up to cycle 25 (Arm C). The primary endpoint is EFS as assessed by the investigator, between Arm A and C, defined as the time from randomization to the earliest of recurrence of high-grade disease, progression of disease, persistence of CIS, or death. Key secondary endpoints include EFS as assessed by the investigator between Arm B and Arm C.

About Sasanlimab

Sasanlimab is a humanized immunoglobulin G4 mAb that binds to human programmed death-1 (PD-1) to block its interaction with PD-1 and PD-L1/PD-L2. PD-1 is a protein expressed on T cells, dendritic cells, natural killer cells, macrophages, and B cells, that functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands and may play an important role in tumor evasion from host immunity. It can be administered through a once every four weeks subcutaneous injection by prefilled syringe (2mL).

In early-stage clinical studies, sasanlimab administered at 300 mg SC every four weeks showed clinical efficacy in advanced solid tumors and advanced urothelial cancer. In addition to NMIBC, sasanlimab is being evaluated in several ongoing clinical trials with other novel combinations.

About Pfizer Oncology

At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world's most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.

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Top 10 Genitourinary Cancer Advances In 2024

A recap of key breakthroughs this year in the field of genitourinary cancer.

Lung cancer and lung disease, generative AI: © Royalty-Free - stock.Adobe.Com

New FDA approvals, pivotal clinical trial results, and innovative treatment strategies emerged in the field of genitourinary cancers in 2024. Here are 10 of the top developments from the field this year:

In March 2024, the FDA approved nivolumab (Opdivo) in combination with cisplatin and gemcitabine as a first-line treatment for adults with unresectable or metastatic urothelial carcinoma. Data from the phase 3 CheckMate-901 study (NCT03036098) supported the approval as the addition of nivolumab to chemotherapy led to higher objective response rates (ORR), including a greater proportion of complete responses, and a longer median duration of response vs chemotherapy alone.

In January 2024, the FDA approved erdafitinib (Balversa) for adult patients with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations, following progression on prior systemic therapy, as supported by data from the THOR study (NCT03390504).

In the phase 3 NIAGARA trial (NCT03732677), the combination of neoadjuvant durvalumab (Imfinzi) plus chemotherapy, followed by adjuvant durvalumab, led to significantly improved rates of event-free survival and overall survival (OS) in patients with cisplatin-eligible muscle-invasive bladder cancer, vs neoadjuvant chemotherapy plus placebo. These benefits observed in the study were reached without affecting patients' ability to undergo radical cystectomy.

An experimental immunotherapy, cretostimogenegrenadenorepvec showed promise in the phase 3 BOND-003 trial (NCT04452591) with 112 patients with high-risk Bacillus Calmette-Guérin-unresponsive non–-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ. Sustained and durable CRs over 12 months with a CR rate of 75.2% were seen, according to an interview between Targeted OncologyTM and Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic in Phoenix, Arizona.

Belzutifan (Welireg) showed a significant benefit in progression-free survival (PFS) and ORR when compared with everolimus among patients with advanced clear cell renal cell carcinoma (RCC) previously treated with immune checkpoint and antiangiogenic therapies, according to the results of the phase 3 LITESPARK-005 study (NCT04195750).

The biologics license application (BLA) submission of TLX250-CDx (Zircaix, 89Zr-DFO-girentuximab) for the FDA was completed in June 2024. TLX250-CDx, an investigational radiodiagnostic PET being developed for the characterization of renal masses as clear cell RCC, was studied in the phase 3 ZIRCON study (NCT03849118), and data from this trial support the BLA.

Nadofaragenefiradenovec-vncg (Adstiladrin) is the first FDA-approved intravesical gene therapy for adults with NMIBC who are no longer responsive to standard treatments. This therapy is now available nationwide, with healthcare providers able to prescribe it for patients with NMIBC and carcinoma in situ, with or without papillary tumors, while the ABLE-41 U.S. Study (NCT06026332) continues to evaluate its effectiveness.

A real-world study conducted by researchers at Fox Chase Cancer Center suggests that treatment recommendations for Black and White patients with metastatic RCC should be the same, with immune checkpoint inhibitor–-based therapy (ICI) offered to both groups. The study found that ICI was equally effective as a frontline treatment for both Black and White patients, with both groups experiencing improved real-world PFS vs those treated with sunitinib (Sutent).

TPST-1120, a first-in-class oral inhibitor of PPAR-α, was found to be well tolerated both as monotherapy and in combination with nivolumab (Opdivo) in patients with PD-1 inhibitor–-refractory cancers, including RCC. In the combination arm, 20% of patients showed an ORR, with 30% response in those receiving 400 mg or higher of TPST-1120 twice daily, while 53% of patients in the monotherapy arm achieved stable disease.

The combination of pembrolizumab (Keytruda) and cabozantinib (Cabometyx) showed promising preliminary efficacy and a manageable toxicity profile in patients with metastatic RCC, as demonstrated in a phase 1/2 trial (NCT03149822). Among the 38 evaluable patients, the ORR was 65.8%, with a median PFS of 10.45 months and a median OS of 30.81 months at a median follow-up of 23.5 months.

Each of these developments offers new avenues for treatment and improved patient outcomes for patients with genitourinary cancers.

Ductal Carcinoma In Situ (DCIS) Treatment

Content

Rosso KJ, Weiss A, Thompson AM. Are There Alternative Strategies for the Local Management of Ductal Carcinoma in Situ? Surg Oncol Clin N Am 27(1):69-80, 2017.

Thompson AM, Clements K, Cheung S, Pinder SE, Lawrence G, Sawyer E, Kearins O, Ball GR, Tomlinson I, Hanby A, Thomas JSJ, Maxwell AJ, Wallis MG, Dodwell DJ; Sloane Project Steering Group (NHS Prospective Study of Screen-Detected Non-invasive Neoplasias). Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project. Eur J Cancer. 2018 Aug 6;101:210-219.

Maxwell AJ, Clements K, Hilton B, Dodwell DJ, Evans A, Kearins O, Pinder SE, Thomas J, Wallis MG, Thompson AM; Sloane Project Steering Group. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ. Eur J Surg Oncol. 2018 Apr;44(4):429-435.

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