The Lynx Group
Cholangiocarcinoma News

Benefits of Lenvatinib plus Pembrolizumab in Solid Tumors, Including Biliary Tract Cancer

2020 Year in Review: Cholangiocarcinoma — December 19, 2020

First results of the multicohort phase 2 LEAP-005 study suggest that lenvatinib plus pembrolizumab combination immunotherapy has promising antitumor activity in patients with biliary tract cancer.

One year after the FDA approved the combination of lenvatinib (Lenvima), a multikinase inhibitor, plus the immunotherapy pembrolizumab (Keytruda), a PD-1 inhibitor, for the treatment of patients with advanced endometrial cancer that is not microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), the LEAP-005 study results showed that several other advanced solid tumors, including biliary tract cancer, may also respond to this combination. The LEAP-005 study results were presented at this year’s virtual meeting of the European Society for Medical Oncology (ESMO).

These first results of the phase 2 LEAP-005 study, an open-label, multicohort clinical trial of lenvatinib plus pembrolizumab, were presented as a late-breaking abstract at the ESMO meeting. A total of 187 patients aged ≥18 years with 1 of 6 advanced solid tumors were studied by Zarnie Lwin, MBBS, Senior Staff Specialist, Medical Oncology, Cancer Care Services, Department of Medical Oncology, University of Queensland, Herston, Australia, and colleagues. The 6 solid tumors were triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC that is not MSI-H or dMMR), glioblastoma multiforme, and biliary tract cancer (excluding ampulla of Vater).

Study participants received lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks. Treatment was continued for 35 weeks or until disease progression was confirmed or toxicity was unacceptable. The tumor cohorts received the combination therapy as second or third line for TNBC, fourth line for ovarian cancer, third line for gastric cancer, and third line for CRC (non–MSI-H/dMMR), second line for glioblastoma multiforme, and second line for biliary tract cancer.

Each cohort included 31 patients (except 32 patients for the CRC cohort). The intention was to expand the number of patients ≤100 for cohorts in which sufficient efficacy was observed. The primary end points were objective response rate (ORR) by safety and blinded central review per Response Evaluation Criteria in Solid Tumors version 1.1.

Efficacy

As of April 10, 2020, the data cutoff date, median follow-up was 8.6 months (range, 1.9-13.1 months). The efficacy was encouraging across all tumor types. The ORRs ranged from 10% to 32% in the following tumor types: 10% in gastric cancer (95% confidence interval [CI], 2-26) and biliary tract cancer (95% CI, 2-26); 16% (95% CI, 6-34) in glioblastoma multiforme; 22% (95% CI, 9-40) in CRC; 29% (95% CI, 14-48) in TNBC; and 32% (95% CI, 17-51) in ovarian cancer.

Disease control rates were 48% in gastric cancer, 68% in biliary tract cancer, 58% in glioblastoma multiforme, 47% in CRC, 58% in TNBC, and 74% in ovarian cancer. Median duration of response was 3.2 months in glioblastoma multiforme, 5.3 months in biliary tract cancer, and not reached in the other cohorts at the time of cutoff. The longest duration of response observed was 10.4+ months, which was seen in a patient with CRC.

Safety

The safety of lenvatinib plus pembrolizumab was deemed manageable. The most common grade ≥3 treatment-related adverse events were reported in patients with ovarian cancer (68%). The least common adverse events were reported in patients with glioblastoma multiforme (35%). In patients with other tumor types, grade ≥3 adverse events were 42% in gastric cancer, 48% in biliary tract cancer, 50% in CRC, and 55% in TNBC.

The proportion of patients discontinuing treatment because of adverse events was also highest in patients with ovarian cancer (13%), followed by TNBC (10%) and CRC (9%); discontinuation rate was 6% for patients with gastric cancer, glioblastoma multiforme, and biliary tract cancer.

This study is ongoing and, considering the promising activity observed across the 6 tumor types, all cohorts are being expanded to include ≤100 patients per cohort.

Source: Lwin Z, et al. Ann Oncol. 2020;38(4_suppl). Abstract LBA41.

Related Items

A Phase 1/2 Study of the Safety and Efficacy of the Arginase Inhibitor INCB001158 plus Chemotherapy in Patients with Advanced Biliary Tract Cancer
2021 Year in Review: Cholangiocarcinoma
Results of an open-label, phase 1/2 study indicate that addition of INCB001158 to the standard gemcitabine/cisplatin backbone was tolerable, did not result in significant additional toxicity, and showed modest clinical activity in the biliary tract cancers cohort.
Lenvatinib plus Pembrolizumab for Patients with Previously Treated Biliary Tract Cancers in the Multicohort Phase 2 LEAP-005 Study
2021 Year in Review: Cholangiocarcinoma
Results of the phase 2 LEAP-005 study suggest that lenvatinib plus pembrolizumab shows promising antitumor activity and manageable toxicity in previously treated patients with advanced biliary tract cancers.
Zanidatamab (ZW25) in HER2-Positive Biliary Tract Cancers: Results from a Phase 1 Study
2021 Year in Review: Cholangiocarcinoma
Results from a first-in-human, phase 1 study have shown that the bispecific HER2-targeted antibody zanidatamab is well-tolerated and has antitumor activity in patients with HER2-overexpressing biliary tract cancers.
Phase 2a MyPathway Results of Pertuzumab plus Trastuzumab for the Treatment of HER2-Positive Metastatic Biliary Tract Cancer
2021 Year in Review: Cholangiocarcinoma
Results of an ongoing, phase 2a, multiple-basket study (MyPathway) showed that dual HER2-targeted therapy with pertuzumab plus trastuzumab was well-tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer.
Liposomal Irinotecan in Combination with 5-Fluorouracil and Leucovorin for Patients with Metastatic Biliary Tract Cancer After Progression on Gemcitabine plus Cisplatin: A Multicenter, Comparative, Randomized, Phase 2b Study (NIFTY)
2021 Year in Review: Cholangiocarcinoma
Results of the NIFTY trial demonstrated that liposomal irinotecan plus 5-fluorouracil and leucovorin significantly improved efficacy outcomes compared with 5-fluorouracil plus leucovorin alone in patients with biliary tract cancer who progressed on prior gemcitabine/cisplatin, with a manageable adverse event profile.
Liposomal Irinotecan plus 5-Fluorouracil/Leucovorin or Gemcitabine/Cisplatin in Patients with Advanced Biliary Tract Cancer (NIFE Trial)
2021 Year in Review: Cholangiocarcinoma
The phase 2 NIFE study compared a liposomal irinotecan plus fluorouracil and leucovorin regimen with standard-of-care gemcitabine/cisplatin in patients with advanced biliary tract cancer.
Does Adjuvant Chemoradiation Benefit Patients with Lymph Node–Positive Biliary Tract Cancer? A Secondary Analysis of SWOG S0809
2021 Year in Review: Cholangiocarcinoma
Results of the secondary analysis of the SWOG S0809 trial indicate that nodal status did not impact survival outcomes achieved with adjuvant chemoradiation postresection in patients with extrahepatic CCA or gallbladder cancer.
Role of ctDNA to Predict Risk for Recurrence Following Potentially Curative Resection of Biliary Tract and Pancreatic Malignancies
2021 Year in Review: Cholangiocarcinoma
Results of a pilot study demonstrate the feasibility of ctDNA testing and the prognostic value of ctDNA following potentially curative resection in patients with pancreatic/biliary tract malignancies.
Efficacy and Safety of Nab-Paclitaxel plus Gemcitabine/Cisplatin in Korean Patients with Advanced Biliary Tract Cancers
2021 Year in Review: Cholangiocarcinoma
Real-world retrospective evidence from Korean patients with advanced biliary tract cancer indicates that efficacy and safety with nab-paclitaxel plus gemcitabine/cisplatin combination were consistent with those previously reported in clinical trials.
First-Line Immunotherapy plus Chemotherapy Significantly Improves Survival in Advanced Biliary Tract Cancer
Web Exclusives
On October 25, 2021, AstraZeneca announced high-level positive results from the phase 3 clinical trial TOPAZ-1, demonstrating that adding the immunotherapy durvalumab (Imfinzi) to first-line standard-of-care chemotherapy leads to a statistically significant and clinically meaningful overall survival (OS) benefit versus chemotherapy alone in patients with advanced biliary tract cancer.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: