Med

Integrating CTLA-4/PD-1 blockade into cervical cancer management: Results of COMPASSION-16

Although there is anti-tumor efficacy of dual CTLA-4/PD-1 blockade in advanced/recurrent cervical cancer, it is unclear whether combination with chemotherapy is synergistic. In COMPASSION-16, Wu et al. demonstrated improved survival outcomes of cadolinimab plus chemotherapy compared to chemotherapy alone for first-line systemic therapy for advanced/recurrent cervical cancer, suggesting a potential role of bispecific CTLA-4/PD-1 inhibitors in the frontline setting.

Immunotherapy in locally advanced cervical cancer: Integrating KEYNOTE-A18 into management strategies

In locally advanced cervical cancer (LACC), the benefit of PD-1 blockade was unknown. In KEYNOTE-A18, Lorusso et al.

Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells

Ovarian cancer (OC) poses a significant challenge for conventional chimeric antigen receptor-engineered T (CAR-T) cell therapy, due to frequent recurrence linked to tumor heterogeneity, platinum resistance, immune evasion, and an immunosuppressive tumor microenvironment (TME). Here, we analyze primary OC patient samples and identify a unique opportunity for allogeneic CAR-NKT ( Compared to conventional CAR-T cells, These findings underscore the unique efficacy and safety advantages, as well as the off-the-shelf potential of Major funding was provided by the California Institute for Regenerative Medicine (CIRM).

Photodynamic therapy for high-grade squamous intraepithelial lesions: A randomized controlled trial

Ablative/excisional surgery is the recommended therapy for cervical high-grade squamous intraepithelial lesions (HSILs) but is associated with cervical damage and elevated risk of complications upon subsequent pregnancies. This multicenter, randomized, controlled trial compared APL-1702 (2-g ointment containing 5% hexaminolevulinate; photoactivated at 125 J/cm A total of 402 women were enrolled. The 6-month response rate was 41.1% (104/253) in the APL-1702 group versus 21.7% (28/129) in the placebo group (p < 0.001). The HPV16/18 clearance rates were 31.4% (49/156) and 15.4% (12/78) in the APL-1702 and placebo groups, respectively (p = 0.011). The rates of treatment-emergent adverse events were 56.8% (151/266) and 56.0% (75/134) in the APL-1702 and placebo groups, respectively. At the end of the 6-month extension period, 54.9% (56/102) of the patients who responded at the end of the 6-month treatment period maintained a response. APL-1702 significantly increased the 6-month response rate in patients with cervical HSILs versus placebo control, with a favorable safety profile. This trial was sponsored by Asieris Pharmaceuticals (Shanghai, China).

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial

It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC). In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. 205 patients were randomized to receive IBI310-sintilimab (n = 103) or placebo-sintilimab (n = 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p = 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2 months (95% CI: 2.8-6.2), respectively (hazard ratio [HR] = 0.91, 95% CI: 0.65-1.27; p = 0.58). The median OSs were 13.9 months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2 months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR = 1.12, 95% CI: 0.79-1.58; p = 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%). Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC. This work was funded by Innovent Biologics (Suzhou).

Targeting the glucocorticoid receptor as a therapeutic strategy for ovarian cancer: The ROSELLA study

The ROSELLA trial tested the combination of intermittently dosed relacorilant, a novel glucocorticoid receptor antagonist, plus nab-paclitaxel versus nab-paclitaxel alone in recurrent platinum-resistant ovarian cancer (PROC).

Transforming ovarian cancer care by targeting minimal residual disease

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Photodynamic therapy: An alternative technique to cervical conization for cervical dysplasia

Predominantly prevalent in women of reproductive age, high-grade cervical dysplasia and its subsequent management can be challenging and significantly impact fertility goals. In a randomized controlled phase III trial, Chen et al. demonstrate that photodynamic therapy with APL-1702 is better than placebo for regression of CIN2 lesions and has a good safety profile; further investigations are warranted before it can enter standard clinical practice.

Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial

The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43 months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. This investigator-initiated trial was funded by Merck.

Maternal to fetal transmission of cancer: implications for molecular tumor testing, immune regulation, and pediatric malignancies

Molecular tumor testing has transformed the treatment of patients with malignancies and is helping catalyze the development of novel therapeutic strategies. In a recent issue of

Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis

Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. In this phase 1b study, registered at Clinical. gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n = 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8 months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).

Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer?

Recurrent endometrial cancer (EC) remains a therapeutic challenge despite advancements in personalized medicine. SIENDO trial showed the potential clinical benefit of selinexor in patients with TP53 wild-type advanced/recurrent EC. The quest for novel therapeutic avenues and approaches continues as researchers seek a glimmer of hope in an area of uncertainty.