PMV, Genmab, Seagen & More Present New Clinical Data at ASCO
More oncology firms presented updates and data in their respective cancer research and development programs at the 2022 American Society of Clinical Oncology (ASCO) annual meeting this week, including research in cervical cancer, solid tumors and head and neck cancer. Continue reading for more details and insight.
PMV Shares Early Data From Phase I/II Trial On Solid Tumor Therapy
Preliminary results from PMV Pharmaceuticals' Phase I/II Pynnacle trial of PC14586 in patients with advanced solid tumors demonstrated the drug's efficacy across different types of tumors. The participants were diagnosed with advanced solid tumors that harbor a p53 Y220C mutation. PC14586 is a first-in-class, precision oncology, small molecule that can target the said mutation.
In the oral presentation at ASCO, PMV shared that eight of 25 patients who received an initial daily dose of 1,150 mg and up of PC14586 achieved an overall response rate of 32%. Of these eight, six reported confirmed partial responses, while two reported unconfirmed partial responses. Across all dose cohorts, the ORR was 24%, or eight out of 33. Responses were seen across six different types of tumors, including ovarian, breast, prostate, endometrial, pancreatic and small cell lung cancer. The maximum tolerated dose was 1,500 mg two times a day.
Less than 15% of the patients reported treatment-emergent adverse events, including fatigue, nausea and vomiting, anemia, blood creatinine increase, AST increase and ALT increase. The company is now enrolling participants for the dose cohort under the maximum tolerated dose to determine the next steps for Phase II.
"These encouraging Phase 1 safety and preliminary efficacy data provide proof of concept for PC14586 as monotherapy to selectively reactivate p53 across multiple tumor types," Dr. Leila Alland, the chief medical officer of PMV, said in a statement.
Phase I of the Pynnacle trial is expected to end in the second half of 2022, while the Phase II portion is touted to begin in early 2023.
Genmab, Seagen Cervical Cancer Candidate Misses Secondary Endpoint
Interim results from Genmab and Seagen's innovaTV 205 trial studying a candidate drug for recurrent or metastatic cervical cancer (r/mCC) showed that the drug failed to achieve the median durability of response endpoint at the average 19-month follow-up period.
The trial is evaluating Tivdak (tisotumab vedotin) in combination with pembrolizumab in patients with r/mCC who have not undergone systemic therapy. This dose-expansion cohort involved 33 patients.
While results for MDR were not favorable, tisotumab vedotin demonstrated a 41% objective response rate, with 16% of participants achieving complete responses and 25% achieving partial responses. The median progression-free survival was 5.3 months.
Tisotumab vedotin is approved in the U.S. for patients with previously treated r/mCC. This cohort extends assessments to those who haven't received any prior treatment.
"With Genmab, we will continue to investigate tisotumab vedotin in combination with other therapies because there is still an unmet need for more effective first-line treatment for advanced cervical cancer patients. We're also researching innovative new tools to help increase awareness of the disparities and unmet needs that cervical cancer patients experience in order to better support this community in the future," said Dr. Majorie Green, senior vice president and head of late-stage development at Seagen.
ChemoCentryx Posts Safety Outcomes From Phase I Trial On AST
Interim results from ChemoCentryx's ongoing Phase I clinical trial of CCX559 for advanced solid tumors showed the drug to be generally safe, with no dose-limiting toxicities.
The first-in-human dose-escalation study involves 13 patients, 10 of whom have had at least two prior lines of systemic therapy. Participants were divided into 30 mg, 60 mg, 120 mg and 180 mg dose cohorts, with the drug given once a day.
So far, there haven't been any DLTs or treatment-related serious adverse events reported. The trial's key objectives are to determine tolerability and safety, as well as establish the dosage level to be used for the upcoming Phase II/III clinical study. At its ASCO presentation, ChemoCentryx said that 120 mg once a day is a therapeutically relevant dose.
The company expects to present more findings from this Phase I trial at other oncology conferences throughout 2022. ChemoCentryx plans to bring CCX559 into a Phase IB/II study to evaluate the drug's anti-tumor effects in the second half of the year.
eFFECTOR Solid Tumor Candidate Demonstrates Safety
eFFECTOR Therapeutics reported positive initial results from its Phase I/II clinical study of zotatifin in patients diagnosed with solid tumors.
Data presented at ASCO from the dose-escalation trial showed the eIF4A inhibitor to be generally well-tolerated, with mostly mild treatment-emergent adverse events (TEAEs) that are reversible and easily managed. TEAEs included anemia, diarrhea, fatigue, nausea and vomiting. None of the 25 trial participants who received the recommended Phase II dose exhibited drug-related Grade 3, 4 or 5 TEAEs.
The study has a total of 54 patients, 37 of whom were part of the Phase I dose-escalation portion, while the remaining 17 were based under the Phase II expansion portion. In part one, the primary objectives are to assess zotatifin's safety and tolerability as a monotherapy and to define Phase II dosing. In part two, the goal is to evaluate the drug's preliminary antitumor activity as a monotherapy and combination therapy.
eFFECTOR has expanded the cohort to evaluate the drug in combination with fulvestrant in ER+ breast cancer patients ages 18 years and up. It will also launch a new cohort for zotatifin plus fulverstrant in ER+ breast cancer patients with Cyclin D1 amplification soon.
Proposed Therapy For Head & Neck Cancer Safe As Monotherapy and With Keytruda
In its poster presentation at ASCO, Cue Biopharma shared that its candidate drug for recurrent/metastatic HPV16+ head and neck cancer was found to be generally safe as monotherapy and if used in combination with pembrolizumab (Keytruda).
Initial results from its Phase I dose-escalation trial of CUE-101 demonstrated a 43% clinical benefit rate, including a confirmed durable partial response at 42 weeks and six stable disease responses with a median duration of 23.9 weeks. The drug also showed a favorable tolerability and safety profile, although the maximum tolerated dose has not yet been set as of this writing.
CUE-101 is a novel HPV16 E7-pHLA-IL2-Fc fusion protein that works by presenting "cues" to T-cells to selectively stimulate tumor-specific cytotoxic T cells against cancer, all while reducing or avoiding the negative effects of IL-2 therapy. It is part of the CUE-100 series, which comprises Fc-fusion biologics that combine peptide-MHC molecules with rationally engineered IL-2 molecules. The result is a biologic that can selectively target, activate and expand a patient's range of tumor-specific T cells. The objective is to reduce dose-limiting toxicities that are typically linked with current IL-2-based treatments.