Several new clinical trials investigating novel drugs in gynecologic cancers have opened in recent months. Maybe one of your patients could benefit from taking part.
Ovarian, clear-cell, endometrial, or cervical cancer. Patients who have received one of these diagnoses and have run out of appropriate treatment options can join a phase 2, open-label study testing the experimental checkpoint inhibitor vudalimab (XmAb20717, developed by Xencor).
This clinical trial has two stages. In the first stage, 10 people with each type of cancer will receive vudalimab by intravenous (IV) infusion every 2 weeks. If at least two patients with a particular diagnosis respond within 12 weeks, researchers will enroll 20 more people into that group. If fewer than two people respond, no more patients will be enrolled for that cancer type. The sole outcome measure is objective response rate (ORR) over 12 weeks. Overall survival (OS) and quality of life (QoL) will not be tracked. Sites in California, Nevada, and New York started recruiting in July 2022. The goal is to enroll 150 participants. More details at clinicaltrials.gov
Vudalimab is a humanized bispecific monoclonal antibody that simultaneously targets PD-1 and CTLA-4 and binds preferentially to PD-1/CTLA-4 dual-positive cells (J Clin Oncol, June 2022 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS5097).
Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, who is not involved in this trial, was asked to comment.
“[This is] an interesting study examining the potential utility in gynecologic malignancies of a novel bispecific antibody targeting two relevant immune checkpoints,” Markman said. “Of note, while checkpoint inhibitor therapy has been revealed to be clinically relevant in specific subsets of patients in endometrial and cervix cancer, this is not the case [to date] in ovarian cancer.”
Recurrent, metastatic, or persistent cervical cancer not treated with systemic therapy except as part of chemoradiotherapy and not amenable to curative treatment. Adults with this type of cervical cancer can also enter a phase 2, open-label study of vudalimab, this time in Texas. For approximately 1 year, patients will receive IV infusions of vudalimab every other week. The study opened in August 2022 at MD Anderson Cancer Center in Houston and seeks to enroll 140 participants with a range of rare cancers. Once again, the sole outcome measure is ORR, but in this trial, OS is a secondary outcome. QoL will not be assessed. More details at clinicaltrials.gov
High-grade serous ovarian, primary peritoneal or fallopian-tube cancer. Individuals with one of these cancers who have not received treatment are being recruited for a randomized, open-label, phase 2 study of the novel antibody MK-4830 in combination with pembrolizumab (Keytruda) and standard-of-care therapy.
Before their surgery, all patients in the trial will receive thrice-weekly infusions of pembrolizumab, paclitaxel (Taxol), and carboplatin (Paraplatin) or docetaxel (Taxotere); after surgery, bevacizumab (Avastin, biosimilars) will be added to the mix. People in the investigational arm will also receive IV infusions of MK-4830 every 3 weeks. Study sites in the US (New Jersey, New York, and South Dakota) and eight other countries opened in July 2022 in the hope of enrolling 160 participants. The primary outcome is change from baseline in circulating tumor DNA. OS and QoL will not be measured. More details at clinicaltrials.gov
MK-4830 is a novel first-in-class human IgG4 monoclonal antibody that targets the immunoglobulin-like transcript 4 receptor. It was reported to have antitumor activity in combination with pembrolizumab in solid tumors (Clin Cancer Res. 2022;28:57–70. https://doi.org/10.1158/1078-0432.CCR-21-2160)
Markman commented that this trial was “a potentially important study seeking to explore the potential clinical relevance of a novel combination immunotherapy approach in the management of ovarian cancer.”
Advanced/metastatic, pretreated, platinum-resistant epithelial ovarian, primary peritoneal, or fallopian-tube cancer. People with these types of cancer and no/minor peripheral neuropathy are eligible to participate in a nonrandomized, open-label, phase 2 study to see whether disease progression can be slowed by treatment with the novel antibody therapy navicixizumab (developed by Mereo). A previous phase 1 trial yielded a 43% ORR in a similar patient population in which navicixizumabin was used in combination with paclitaxel; this is the first phase 2, monotherapy study involving such patients.
All participants will receive navicixizumab infusions every 2 weeks. If they “appear to benefit,” they will continue taking the drug until the tumor progresses, side effects become intolerable, or withdrawal occurs for another reason. Sites in Arkansas, Georgia, Louisiana, New York, Ohio, and Tennessee started recruiting for the trial’s 180 participants across four different cancers in August 2022. ORR and progression-free survival (PFS) are primary endpoints, OS is a secondary endpoint, and QoL will not be tracked. More details at clinicaltrials.gov
Navicixizumab is described by the company as an anti-DLL4/VEGF bispecific antibody designed to inhibit both Delta-like ligand 4 (DLL4) in the Notch cancer stem cell pathway, as well as vascular endothelial growth factor (VEGF) and thereby induce potent antitumor responses while mitigating certain angiogenic-related toxicities.
“[This is] an interesting trial exploring the activity of a novel bispecific antibody targeted at checkpoint inhibition in cervix cancer,” commented Markman.
Nonresectable, platinum resistant/refractory ovarian, primary peritoneal, or fallopian-tube cancer. Adult patients with one of these cancers who have been treated with at least three lines of therapy can join a randomized, open-label, phase 3 study testing the effectiveness of olvimulogene nanivacirepvec (Olvi-Vec, from Genelux).
Olvi-Vec is an oncolytic vaccinia virus–based immunotherapy designed to activate the immune system and resensitize tumor cells to chemotherapy.
All participants will receive platinum-doublet chemotherapy plus bevacizumab until the disease progresses or the patient can no longer tolerate the therapy. In the experimental arm, at least 4 weeks prior to the start of chemotherapy, patients will receive intraperitoneal infusions of Olvi-Vec for 2 days. PFS is the primary endpoint. OS is a secondary endpoint. QoL will not be recorded. The research site at AdventHealth Cancer Institute in Orlando, Forida, started recruiting 186 participants in August 2022.. More details at clinicaltrials.gov
Advanced/metastatic ovarian or endometrial cancer. Adult patients with this cancer can join an open-label phase 2 trial testing the antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd).
Dato-DXd is a specifically designed TROP2-directed deruxtecan ADC being jointly developed by AstraZeneca and Daiichi Sankyo. Phase 1 trial results from small groups of patients with a variety of solid tumors (including lung cancer) are already available; this study moves the product into phase 2.
In this trial, participants will receive IV infusions of Dato-DXd for approximately 1 year. One group will receive the product as monotherapy, a second in combination with carboplatin (Paraplatin), and a third group in combination with AZD5305, an experimental PARP inhibitor. One site in California and two in Taiwan began recruiting the planned 531 trial participants across five different cancers in September 2022; centers in 11 more US states and 12 additional countries are planned. The primary outcomes are ORR and adverse-event profile; OS and QoL are not being assessed. More details at clinicaltrials.gov
Markman viewed this study as “a quite relevant examination of a potential role for a novel antibody-drug conjugate in gynecologic malignancies.”
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
Markman has no involvement with any of these trials. He is a regular contributor to Medscape with his Markman on Oncology series. He has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.