The phase 2 LOTIS-9 study of loncastuximab tesirine-lpyl combined with rituximab has been initiated with the dosing of the first patient with previously untreated diffuse large B-cell lymphoma.
The combination of loncastuximab tesirine-lpyl (Zynlonta) and rituximab (Rituxan), or the Lonca-R regimen, has been dosed in the first patient with previously untreated diffuse large B-cell lymphoma (DLBCL). The treatment strategy is a part of the ongoing phase 2 LOTIS-9 clinical trial (NCT05144009), according to an announcement by ADC Therapeutics SA.1
LOTIS-9 is an open-label study that will assess the efficacy and tolerability of a response-adapted treatment of Lonca-R in unfit and frail patients with previously untreated DLBCL who are in ineligible for treatment with standard rituximab plus cyclophosphamide 400 mg/m2 during dose 1 (D1); doxorubicine 25 mg/m2 D1; vincristine 1 mg total dose D1, and prednisolone 40 mg/m2 by oral route from D1 to D5 (R-mini-CHOP).1,2
Trial Name: A Phase 2 Open-label Study of Loncastuximab Tesirine in Combination With Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Patients With Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9)
ClinicalTrials.gov Indentifier: NCT05144009
Completion Date: February 18, 2030
Recruitment Status: Recruiting
Sponsor: ADC Therapeutics S.A.
Recruitment Contact: 954-903-7994, clinical.trials@adctherapeutics.com
“Unfit, elderly, and frail DLBCL patients represent a growing population for which new treatments are greatly needed. These patients are often unable to tolerate the standard of care R-CHOP or even a modified R-CHOP regimen and they are excluded from many first-line studies,” said Joseph Camardo, MD, chief medical officer of ADC Therapeutics, in a press release. “Following results from the safety run-in of our LOTIS-5 phase 3 confirmatory trial that demonstrated the tolerability and additive efficacy of Zynlonta in combination with rituximab, we are pleased to be assessing the combination in the LOTIS-9 trial in the first-line DLBCL setting for these particular patients.”
Cohort A of the LOTIS-9 still will assess efficacy in unfit patients and Cohort B will evaluate tolerability in frail patients. Treatment in both cohorts will consist of rituximab 375 mg/m2 on day 1 of cycle 1 and loncastuximab tesirine 150 µg/kg on day 2 of cycle 1. During cycle 2, Lonca-R will be administered as rituximab 375 mg/m2 and loncastuximab tesirine 150 µg/kg on day 1. Lonca-R will then be administered as rituximab 375 mg/m2 and loncastuximab tesirine 75 µg/kg on during cycles 3 thereafter. The protocol states that subcutaneous rituximab at 1400 mg/dose may be used during cycle 2 and beyond.2
LOTIS-9 is evaluating the primary end points of complete response (CR) rate in the overall population as well as the percentage of patients completing 4 cycles of treatment in cohort B. The secondary end points of the study include overall response rate, 2-year progression-free survival, 3-year overall survival, duration of response, the number of patients with treatment-emergent adverse events, the number of patients with clinically significant change from baseline in ECOG performance status, and the presence of loncastuximab tesirine antibodies.
During the exploratory stage of the study, 80 patients who are aged 80 or older will be enrolled. All patients will be screened using the simplified geriatric assessment (sGA) to determine whether they are unfit or frail.1
To measure the success of the Lonca-R regimen, the first arm will receive the treatment for 3 cycles. Patients who achieve a CR will be given an additional cycle of Lonca-R. In the second arm, patients who achieve a partial response after the first 3 cycles will receive Lonca-R for an additional 3 cycles, which can continue for up to 6 cycles.
Patients are eligible to enroll in the study given they have a pathologic diagnosis of DLBCL that is stage I-IV, measurable disease, an ECOG performance status of 0-2, and adequate organ function. The study is actively recruiting patients who meet the study criteria at sites in Nevada, New York, South Dakota, Texas, and Virginia.2
“We look forward to the continued advancement of our clinical program designed to maximize the potential of Zynlonta and address significant unmet medical needs for patients with lymphoma around the world,” added Camardo.1
REFERENCES:
1. ADC Therapeutics announces first patient dosed in phase 2 clinical trial of Zynlonta (loncastuximab tesirine-lpyl) in combination with rituximab in first-line diffuse large b-cell lymphoma. News release. ADC Therapeutics SA. July 20, 2022. Accessed July 20, 2022. https://bit.ly/3PESfNd
2. A study of loncastuximab tesirine and rituximab (Lonca-R) in previously untreated unfit/frail participants with diffuse large b-cell lymphoma (DLBCL) (LOTIS-9). ClinicalTrials.gov. Updated July 5, 2022. Accessed July 20, 2022. https://clinicaltrials.gov/ct2/show/NCT05144009
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