Dr Gonzalez-Martin on the Efficacy of TUB-040 in Ovarian Cancer

“In this heavily pretreated patient population, we observed an unconfirmed ORR of 59% and a confirmed ORR of 50%, including 1 complete response.”

Antonio Gonzalez-Martin, MD, the head of the Department of Medical Oncology at Clinica Universidad de Navarra, the director of the Cancer Center Clinica Universidad de Navarra, and an associate professor of medicine at Francis, discussed the key efficacy data from the phase 1/2a NAPISTAR1-01 trial (NCT06303505) of the novel antibody-drug conjugate TUB-040 in patients with platinum-resistant, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Findings from NAPISTAR1-01 presented during the 

 showed that patients who received TUB-040 at the 1.67 mg/kg to 3.3 mg/kg dose range (n = 46) achieved an overall response rate (ORR) of 59% and a confirmed ORR of 50%, including 1 patient with a complete response, Gonzalez-Martin. The disease control rate (DCR) and confirmed DCR were both 96%. He added that the population was heavily pretreated, with 83.6% of patients in the overall population (n = 67) having received prior bevacizumab (Avastin) and 76.1% of patients having received a prior PARP inhibitor.

Gonzalez-Martin noted that responses were observed even in patients who received TUB-040 at lower dose levels. Specifically, patients in the 1.67-mg/kg cohort (n = 10) experienced an ORR of 60%, a confirmed ORR of 40%, and a DCR and confirmed DCR of 90%.

Additional findings presented during the meeting showed that the CA125 response rate across the 1.67-mg/kg to 3.3-mg/kg doses was 81%. Ninety-three percent (n = 25/27) of patients who responded were in an ongoing response at the data cutoff, and 80% (n = 37/46) of patients were remaining on treatment, indicating a durable benefit according to the study authors.

Gonzalez-Martin reported receiving research grants from GSK, Roche, ISCiii, and AECC; having advisor roles with Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, HederaDx, AbbVie/Immunogen, Incyte, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, SOTIO, SUTRO, Seagen, Takeda, Tubulis, and Zalia; providing expert testimony for AstraZeneca, Clovis, GSK, Immunogen, Mersana, MSD, Novocure, PharmaMar, Roche, Takeda, Seagen, and ZaiLab; being the chairman of GEICO; and receiving travel support from AstraZeneca/MSD and GSK.

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Antonio Gonzalez-Martin, MD, discusses the key efficacy findings from the NAPISTAR1-01 trial of TUB-040 in ovarian cancer. 

Dr Gonzalez-Martin on the NAPISTAR1-01 of TUB-040 in Ovarian Cancer

“The focus of our presentation was the dose range from 1.67 mg/kg to 3.3 mg/kg. We included patients with high-risk, high-grade platinum-resistant ovarian cancer who have received up to a maximum of 7 prior lines of therapy, including 5 platinum-[based] and 2 non-platinum–[based treatments]”

Antonio Gonzalez-Martin, MD, the head of the Department of Medical Oncology at Clinica Universidad de Navarra, the director of the Cancer Center Clinica Universidad de Navarra, and an associate professor of medicine at Francis, outlined the key design features of the phase 1/2a NAPISTAR1-01 trial (NCT06303505) of TUB-040 in patients with platinum-resistant ovarian cancer, findings from which he presented during the 

NAPISTAR1-01 was a dose-escalation and -optimization study that examined the novel antibody-drug conjugate (ADC) TUB-040 in patients with histologically confirmed, platinum-resistant, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. The study evaluated TUB-040 at doses ranging from 0.5 mg/kg to 5.3 mg/kg, he added. The focus of the presentation given during ESMO were the 1.67-mg/kg to 3.3-mg/kg cohorts, he noted.

Eligible patients needed to have received a maximum of 5 platinum-based and 2 non-platinum based prior lines of therapy, Gonzalez-Martin said; patients also were required to not have been treated with a prior ADC containing a topoisomerase-I inhibitor payload. An ECOG performance status of 0 or 1 was also required.

The primary end point of the study was safety and tolerability, as well as determining the maximum tolerated dose, Gonzalez-Martin said. Secondary end points included overall response rate per RECIST 1.1 criteria, disease control rate, progression-free survival, and overall survival, he concluded.

Overall, 67 patients received TUB-040 at any dose level. The median exposure to the agent was 161 days (range, 21-462). The median number of prior lines of therapy was 4 (range, 1-7) and the median age was 62.0 years (range, 34.0-81.0).

Antonio Gonzalez-Martin, MD, discusses the design of the NAPISTAR1-01 trial of TUB-040 in ovarian cancer. 

Dr Gonzalez-Martin on the NAPISTAR1-01 Trial of TUB-040 in Ovarian Cancer

Dr Gonzalez-Martin on the Rationale for Targeting NaPi2b in Ovarian Cancer

“TUB-040 is a new ADC with an exatecan payload and a stable linker. [The agent] targets NaPi2b, [which is] a very interesting target in ovarian cancer because it is highly expressed [on cancer cells] and is a transporter.”

Antonio Gonzalez-Martin, MD, the head of the Department of Medical Oncology at Clinica Universidad de Navarra, the director of the Cancer Center Clinica Universidad de Navarra, and an associate professor of medicine at Francisco de Vitoria University, discussed the clinical rationale for targeting sodium-dependent phosphate transport protein 2b (NaPi2b) for the treatment of patients with ovarian cancer.

Patients with platinum-resistant ovarian cancer represent a high unmet need and lack sufficiently active treatments, Gonzalez-Martin began. Exploring treatment with antibody-drug conjugates (ADCs) represents an important area of therapeutic development for these patients, he continued.

The novel ADC TUB-040 could represent a new treatment option for patients with platinum-resistant disease, Gonzalez-Martin noted. The agent is comprised of an exatecan payload and a stable linker and targets NaPi2b, he explained. NaPi2b represents an attractive treatment target in ovarian cancer because it is highly expressed on the cancer cells and is a transporter protein, he added.

, Gonzalez-Martin presented data from the phase 1/2a NAPISTAR1-01 trial (NCT06303505), which was a dose escalation study of TUB-040 in patients with platinum-resistant, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Patients needed to have an ECOG performance status of 0 or 1, have received a maximum of 5 platinum-based and 2 non-platinum based prior lines of therapy, and have no received a prior ADC containing a TOPO-I inhibitor payload in order to be eligible for the study. The objectives of the study included safety and tolerability, determining the maximum tolerated dose, overall response rate per RECIST 1.1 criteria, disease control rate, progression-free survival, and overall survival.

Antonio Gonzalez-Martin, MD, discusses the rationale for targeting NaPi2b in ovarian cancer.

Antonio Gonzalez-Martin, MD, PhD, director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses new long-term progression-free survival (PFS) data from the phase 3 PRIMA trial (NCT02655016) in advanced ovarian cancer.


The randomized phase 3 trial investigated the efficacy of niraparib (Zejula) as a maintenance treatment for patients with stage III or IV ovarian cancer who had previously completed frontline platinum-based chemotherapy.


Updated findings presented at the 2022 ESMO Congress demonstrated that the administration of niraparib improved median progression-free survival (PFS) benefit when compared with placebo, confirming its sustained benefit in reducing the risk of disease progression or death, Gonzalez-Martin states. Compared with the data presented at the 2019 ESMO Congress, which had a median follow-up of 1.2 years, the median follow-up for the updated results was 3.5 years with a data cut-off in November 2021.


These new results show that niraparib reduced the risk of progression or death by 55% in patients with homologous recombination deficiency (HRD) and increased median PFS in that population from 11.2 months to 24.5 months. Similarly, median PFS in the overall population was prolonged from 8.2 months to 13.8 months, reducing the risk of progression or death by 34%, Gonzalez-Martin concludes.

Antonio Gonzalez-Martin, MD, PhD, discusses new long-term progression-free survival data from the phase 3 PRIMA trial in advanced ovarian cancer.

Dr. González-Martín on Updated PFS Data From the PRIMA Trial in Advanced Ovarian Cancer

Antonio González-Martín, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the design of the phase III PRIMA trial (ENGOT-OV26/GOG-3012) in ovarian cancer.

The PRIMA study examined patients with high-grade serous or intermediate-grade stage III or IV cancer with microscopic residual disease after primary debulking surgery, or those who received neoadjuvant chemotherapy, regardless of their residual disease after interval debulking surgery, explains González-Martín. All patients were platinum-sensitive, meaning they achieved a complete response or partial response to chemotherapy.

Tissue was also collected for biomarker analysis and screening using the Myriad myChoice CDx assay to evaluate the homologous recombination deficiency (HRD) status of the tumor.

Patients were randomized 2:1 to receive either niraparib (Zejula) or placebo. Patients were randomized within 12 weeks of finishing the last cycle of chemotherapy. Niraparib was administered once daily for the duration of 36 months or until disease progression. At the initiation of the study, niraparib was administered at a fixed dose of 300 mg once daily, but the protocol was amended to allow patients to receive a lower dose of 200 mg, depending on their baseline body weight and platelet count. This was because data showed that individualized dosing may have a beneficial effect on niraparib-induced myelosuppression, explains González-Martín.

The primary end point of the study is progression-free survival, according to radiological RECIST criteria by blinded independent central review, says González-Martín. A hierarchal analysis of patients with HRD was also performed, concludes González-Martín.

Antonio González-Martín, MD, discusses the design of the PRIMA trial in ovarian cancer.

Dr. Gonzalez-Martin on the PRIMA Trial Design in Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the impact of the phase III PRIMA trial findings on clinical practice in advanced ovarian cancer.

The data from the PRIMA trial taken collectively with the data from phase III PAOLA-1 and VELIA trials are going to change the landscape of ovarian cancer, says Gonzalez-Martin. In PRIMA, niraparib (Zejula) maintenance led to a 38% reduction in the risk of progression or death versus placebo in patients with newly diagnosed, platinum-sensitive advanced ovarian cancer, regardless of biomarker status.

Notably, the PRIMA trial included patients for whom current treatment strategies are not as beneficial, adds Gonzalez-Martin, such as those who received neoadjuvant chemotherapy and bevacizumab (Avastin). These data represent a new standard of care in the overall population of patients with platinum-sensitive ovarian cancer, particularly those mentioned above who derived a significant benefit from niraparib maintenance, concludes Gonzalez-Martin.

Dr. Gonzalez-Martin on the Impact of the PRIMA Trial in Advanced Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the rationale for the phase III PRIMA trial investigating niraparib (Zejula) as maintenance therapy for patients with platinum-sensitive advanced ovarian cancer. 

The majority of patients with advanced ovarian cancer will relapse shortly after completing chemotherapy, says Gonzalez-Martin. Although there are maintenance therapy options, not all patients will benefit from them, he adds.

In the recurrent setting, niraparib has shown an improvement in progression-free survival (PFS) in platinum-sensitive patients regardless of 

 status or homologous recombination deficiency (HRD) status. Therefore, PRIMA was designed to evaluate niraparib as frontline maintenance therapy in patients with high-risk of relapse. 

In the overall population, the median progression-free survival (PFS) was 13.8 months in the niraparib arm compared with 8.2 months in the placebo arm (HR, 0.62; 95% CI, 0.50-0.76; 

 <.001). Notably, HRD-positive patients had a median PFS of 21.9 months with niraparib versus 10.4 months with placebo (HR, 0.43; 95% CI, 0.50-0.76; 

Antonio Gonzalez-Martin, MD, discusses the rationale for the phase III PRIMA trial investigating niraparib (Zejula) as maintenance therapy for patients with platinum-sensitive advanced ovarian cancer.
 

Dr. Gonzalez-Martin on Rationale for Phase III PRIMA Trial in Advanced Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the results of the phase III PRIMA trial in advanced ovarian cancer.

Data presented at the 2019 ESMO Congress demonstrated that frontline maintenance therapy with niraparib (Zejula) improved median progression-free survival (PFS) by 5.6 months versus placebo in patients with newly diagnosed, advanced platinum-sensitive ovarian cancer.

Investigators conducted a hierarchical analysis of patients with homologous recombination deficiency (HRD), which, if positive, would prompt analysis of the overall population, says Gonzalez-Martin. Among patients with HRD, the median PFS was 21.9 months with niraparib versus 10.4 months with placebo (HR, 0.43; 95% CI, 0.50-0.76; 

 <.001). The median PFS in the overall population was 13.8 months in the niraparib arm versus 8.2 months in the placebo arm, which translated to a 38% reduction in the risk of progression or death with the addition of the PARP inhibitor (HR, 0.62; 95% CI, 0.50-0.76; 

Antonio Gonzalez-Martin, MD

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