ASCO GI Round up

OncologyONCOLOGY Vol 35 Issue 2

Phase 2 LEAP-005 Study Yields Promising Results Among Multiple GI Cancer Types

The combination therapy of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) produced positive antitumor outcomes in previously treated patients with advanced gastric cancer, advanced or metastatic microsatellite instability–high (MSI-H) or mismatch repair (MMR)– deficient colorectal cancer, and advanced biliary tract cancer, according to results presented at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The phase 2 LEAP-005 trial (NCT03797326), which aimed to evaluate the safety and efficacy of the lenvatinib/pembrolizumab combination across a number of different solid tumor types, enrolled patients in 7 different cohorts. Only data specific to 3 gastrointestinal cancer types were presented at
the meeting.

Gastric Cancer Cohort Results

The gastric cancer cohort1 enrolled 31 patients (87% male) with metastatic or unresectable gastric cancer who had received at least 2 prior lines of therapy. More than half (58%) of the patients were 65 years or younger, and 71% had a PD-L1 combined positive score of 1.

Patients received lenvatinib 20 mg once daily plus pembrolizumab 200 mg every
3 weeks for up to 35 cycles (approximately 2 years) of pembrolizumab or until disease progression, unacceptable toxicity, or consent withdrawal. In patients who experienced a clinical benefit, treatment with lenvatinib could continue beyond 2 years.

Overall response rate (ORR) and safety were the primary end points of the study, with secondary end points including disease control rate (DCR; which included complete response [CR], partial response [PR], and stable disease [SD]), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Although 19 patients (61%) discontinued treatment, the ORR was 10% (95% CI, 2%-26%) at the time of data reporting. One patient had a CR (3%), 2 had a PR (6%), and 12 patients (39%) had SD, leading to a DCR of 48% (95% CI, 30-67). Median PFS was 2.5 months (95% CI, 1.8-4.2) and median OS was 5.9 months (95% CI, 2.6-8.7). However, median DOR was not reached (range, 2.1+ to 2.3+ months).

Follow-up imaging was done every 9 weeks for 54 weeks, then every 12 weeks until week 102, and every 24 weeks beyond that.

In terms of safety, 90% of patients experienced treatment-related adverse events (TRAEs), 13 (42%) of whom experienced grade 3 to 5 AEs. One patient died as a result of a treatment-related hemorrhage. Immune-mediated AEs were less frequent, found in 8 patients (26%), and included hypothyroidism (n = 5), hyperthyroidism (n = 2), and pneumonitis (n = 1). No infusion-related reactions occurred.

Colorectal Cancer Cohort Results

In the colorectal cancer cohort, 32 patients with advanced or metastatic MSI-H or MMR-deficient colorectal cancer received lenvatinib 20 mg once daily plus pembrolizumab 200 mg every 3 weeks for up to 35 cycles (as in the gastric cancer cohort). Investigators determined that treatment with lenvatinib could continue beyond the 35 cycles in patients who saw clinical benefit.2

The participants’ median age was 56 years, and 91% of patients (n = 29) had received 2 prior lines of therapy.

The study’s primary end points were ORR and safety, with secondary end points including DCR, DOR, PFS, and OS. The median time from first dose to data cutoff was 10.6 months (range, 5.9-13.1).

At data cutoff, the ORR was 22% (95% CI, 9%-40%) and the DCR was 47% (95% CI, 29%-65%). Median PFS was 2.3 months (95% CI, 2.0-5.2) and median OS was 7.5 months (95% CI, 3.9 to not reached [NR]). Median DOR was not reached (2.1+ to 10.4+ months).

Safety data indicated that grade 3 to 5 TRAEs occurred in 16 patients (50%). Three patients discontinued treatment as a result of TRAEs, including a grade 2 ischemic stroke (n = 1), grade 3 increased liver transaminases (n = 1), and grade 5 intestinal perforation (n = 1).

Biliary Tract Cancer Cohort Results

The biliary tract cancer cohort3 included 31 patients with metastatic and/or unresectable disease with progression after 1 prior line of therapy. The treatment schedule was the same as in the gastric and colorectal cancer cohorts, with primary end points of ORR and safety. Secondary end points included the combined DCR, DOR, PFS and OS.

The median time from first dose to data cutoff was 9.5 months (range, 3.1-11.9), with 16 patients remaining on treatment at data cutoff. There were 3 (10%) PRs and 18 (58%) SDs. ORR was 10% (95% CI, 2%-26%), and DCR was 68% (95% CI, 49%-83%). Median DOR was 5.3 months (range, 2.1+ to 6.2). Median PFS was 6.1 months (95% CI, 2.1-6.4) and median OS was 8.6 months (95% CI, 5.6 to NR).

In terms of safety, 30 patients (97%) experienced TRAEs, 15 (48%) of whom had grade 3 or 4 TRAEs. In a presentation on the findings, lead author Luis Villanueva, MD, MSc, noted that the most frequent TRAEs included hypertension (42%), dysphonia (39%), diarrhea (32%), fatigue (32%), and nausea (32%).

Fourteen patients (45%) experienced immune-mediated AEs, including hypothyroidism (n = 11; 36%), hyperthyroidism (n = 2; 6%), and hepatitis (n = 2; 6%). One patient (3%) had an infusion-related reaction, and 2 patients (6%) discontinued treatment due to treatment-related AEs of myocarditis and pyrexia (n = 1 each). No treatment-related deaths occurred.


1. Chung HC, Lwin Z, Gomez-Roca C, et al. LEAP-005: a phase II multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors: results from the gastric cancer cohort. J Clin Oncol. 2021;39(3 suppl; abstr 230). doi:10.1200/JCO.2021.39.3_suppl.230

2. Gomez-Roca C, Yanez E, Im S, et al. LEAP-005: a phase II multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors—results from the colorectal cancer cohort. J Clin Oncol. 2021;39(3 suppl; abstr 94). doi:10.1200/JCO.2021.39.3_suppl.94

3. Villanueva L, Lwin Z, Chung HC, et al. Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase II LEAP-005 study. J Clin Oncol. 2021;39(3 suppl; abstr 321). doi: 10.1200/JCO.2021.39.3_suppl.321

Pembrolizumab-Lanreotide Combination Shows High Response Rates for Patients With GEP-NETs

Roughly 40% of patients with advanced, progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with pembrolizumab (Keytruda) in combination with lanreotide (Somatuline Depot) achieved stable disease, according to results from the phase 1b/2 PLANET clinical trial (NCT03043664).1

In this study, 22 patients with GEP-NETs who had been treated with a median of 2 prior systemic therapies (range, 1-9) were treated with 90 mg of lanreotide and 200 mg of pembrolizumab every 3 weeks until disease progression or intolerable toxicity. A median of 6 doses of pembrolizumab (range, 2-15) and 7 doses of lanreotide (range, 2-15) were administered.

Median age at the time of enrollment was 60.9 years (range, 51.1-82.0). Twelve of the patients were male, and 10 were female. To be eligible for the study, participants were required to have a diagnosis of a nonresectable, recurrent, or metastatic well- or moderately differentiated GEP-NET; disease progression in the last 12 months; receipt of prior somatostatin analogue therapy; a minimum of 1 measurable lesion based on RECIST 1.1 criteria; ECOG performance status of 0 or 1; adequate organ function; and a tumor mitotic rate of 20/10 hpf or less and/or Ki67 index of 20% or less.

The median time since diagnosis for all patients was 5.3 years; 6 patients had received prior locoregional therapy and 3 patients had received prior external beam therapy. Of the 12 tumors that were analyzed, 4 had detectable PD-L1 expression and 11 had tumor-infiltrating

Thirty-nine percent of patients showed stable disease (SD) and 52% of patients had progressive disease (PD). ORR, as measured by irRECIST to better assess the effect of immunotherapeutic agents, included 43% of patients with SD and 48% with PD, while 9% of patients were not evaluable.

Secondary end points were progression-free survival (PFS) and overall survival (OS). The median PFS was 5.4 months (95% CI, 1.7-8.3) and median OS at a median follow-up of 15 months was not reached.

Six of the 22 patients (27.3%) experienced serious treatment-related adverse events (TRAEs) including abdominal pain, pneumonitis, colitis, and hyperglycemia, which were all related to treatment with pembrolizumab. The most common TRAE was hypothyroidism (23%), with other notable TRAEs including colitis (9%), hyperglycemia (14%), and pneumonitis (5%). Three patients (13.6%) discontinued treatment due to AEs.

No new safety signals were identified in the study.


1. Morse M, Halperin DM, Uronis HE, et al. Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET). J Clin Oncol. 2021;39(3 suppl; abstr 369). doi:10.1200/JCO.2021.39.3_suppl.369

Bemarituzumab is Effective for Patients With FGFR2b-Positive GEJ

Results of the phase 2 FIGHT study (NCT03694522), which compared treatment with bemarituzumab plus mFOLFOX6 with treatment of placebo plus mFOLFOX6, demonstrated a 56% reduction with bemariuzumab in the risk of disease progression or death for patients with FGFR2b-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.1

For patients with FGFR2b overexpression via immunohistochemistry (IHC) 2+/3+ at 10% or more (n=96), the median progression-free survival (PFS) was 14.1 months in the bemarituzumab arm versus 7.3 months in the placebo arm (HR, 0.44; 95% CI, 0.25-0.77). The 1-year PFS rates were 57.0% and 26.4% in the combination and placebo arms, respectively.

In those with FGFR2b overexpression via IHC 2+/3+ at 5% or more (n = 118), the median PFS was 10.2 months in the bemarituzumab arm vs 7.3 months with the placebo arm (HR, 0.54; 95% CI, 0.33-0.87). The 1-year PFS rates were 56.3% and 28.6%, respectively.

In the intent-to-treat (ITT) population, the median PFS was 9.5 months and 7.4 months for the combination and placebo arms, respectively (HR, 0.68; 95% CI, 0.44-1.04; P = .0727). The 1-year PFS rates were 52.5% and 33.8%, respectively.

Prior single-agent activity with bemarituzumab in later-line FGFR2b-positive gastric cancer elicited an 18% objective response rate (ORR) with no dose-limiting toxicities.2

This study randomized patients 1:1 to receive bemarituzumab with mFOLFOX6 (n = 77) or placebo/mFOLFOX6 (n = 76), every 2 weeks.

In the ITT population, data showed that the median OS was not reached in the bemarituzumab arm vs 12.9 months in the placebo arm (HR, 0.58; 95% CI, 0.35-0.95; P = .0268). The 1-year OS rates were 65.3% and 56.9%, respectively. The OS benefit with bemarituzumab increased with higher levels of FGFR2b overexpression, similar to findings for PFS.

The ORR in the ITT population was 47% with the combination and 33% with placebo/mFOLFOX6. For patients who had measurable disease at baseline, the ORRs were 53% and 40%, respectively, with a best change in tumor size at –41.7% and –29.9%, respectively. The median time to response was 1.84 months with the combination and 1.67 months with placebo/mFOLFOX6, and the median duration of response was 12.2 months and 7.1 months, respectively.

Grade 3 or higher adverse events (AEs) were seen in 82.9% of patients on bemarituzumab/mFOLFOX6 vs 74.0% of those on placebo/mFOLFOX6, with stomatitis (9.2% vs 1.3%, respectively) and dry eye (2.6% vs 0%, respectively) showing the largest increase in grade 3 or higher AEs with bemaritizumab vs placebo.

Serious AEs occurred in 31.6% of bemarituzumab-treated patients and in 36.4% of patients on the placebo arm. Corneal-related toxicities, which tend to be associated with FGFR inhibitors, occurred in 67.1% and 23.7% of bemarituzumab-treated patients vs 10.4% and 0% of those on placebo/mFOLFOX6, respectively. The mean time to onset of an AE of any grade was 16.1 weeks on bemarituzumab/mFOLFOX6 and 11.6 weeks on placebo. Twenty patients discontinued bemarituzumab treatment due to corneal AEs. Twelve corneal AEs ultimately resolved with a median time to resolution of 27.0 weeks.


1. Wainberg ZA, Enzinge P, Kang Y, et al. A double-blind randomized study of bemarituzumab (bema) plus mFOLFOX6 versus placebo plus mFOLFOX6 as first-line treatment for advanced gastric/gastroesophageal junction cancer (FIGHT). J Clin Oncol. 2021;39(3 suppl; abstr 160). doi: 10.1200/JCO.2021.39.3_suppl.160

2. Catenacci DVT, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol. 2020;38(21):2418-2426. doi:10.1200/JCO.19.01824

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