scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

scholarly journals Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 trial (ORIENT-2)

2021 ◽  
Author(s):  
Jian Ming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Lei Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase

Abstract This randomized, open-label, multi-center phase 2 study (ClinicalTrials.gov, number NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemo in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line (1L) chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with treatment efficacy. The median OS in the sintilimab group was significantly prolonged compared with that of the chemotherapy group, (objective response rates 12.6% and 6.3 %, respectively). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1 %). Patients with high TCR clonality and low mTBI showed the longest median OS (15.0 mo), while patients with low NLR at 6 wk post-treatment had a significantly prolonged median OS compared with those with high NLR. High expression of T-follicular helper cells or activated B-cell signature was significantly associated with longer progression-free survival in the sintilimab group.

Apatinib plus camrelizumab (SHR-1210) for unresectable high-grade osteosarcoma (APFAO) progressing after chemotherapy: A prospective, open label, phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11013-11013 ◽  
Author(s):  
Lu Xie ◽  
Wei Guo ◽  
Jie Xu ◽  
Xin Sun ◽  
Kuisheng Liu ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Bone Lesions ◽  
High Grade ◽  
Open Label ◽  
Recent Success ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
Chemotherapy Patients ◽  
High Grade Osteosarcoma

11013 Background: Results of previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. Given the recent success of immunotherapies, combinations of antiangiogenics with immune checkpoint blockers have become an attractive strategy. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy. Methods: We did this open-label phase 2 trial in Peking University People’s Hospital. We enrolled patients (≥14 years) with advanced osteosarcoma progressing after chemotherapy. Patients received 500 mg apatinib orally taken once daily plus 200 mg camrelizumab intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treatment. This trial is registered with ClinicalTrials.gov. (NCT03359018). Results: We enrolled 41 patients between January 1, and September 4, 2018. 20 (48.8%, 95%CI 32.8%-64.8%) of 41 patients were progression free at 6 months. Until final follow-up, the objective response rate was 21.95% (9/41). And the 6-m PFS rate and 4-m PFS rate were 54.32% (95% CI 37.62%-68.33%) and 70.00% (95% CI 53.24%–81.73%) respectively. Median PFS was 6.50 (95% CI 4.23–7.50) months while the median OS has not reached yet. And there were no statistical differences in the response rates or PFS between different PD-L1 expression groups ( P=0.153 and 0.231). Whereas target lesions with only pulmonary metastasis had obviously longer PFS than those lesions located at other places ( P <0.001). We also summarized all those lesions’ progression patterns as follows: slow pulmonary lesions’ progression(N=7), stable disease with lung but new lesions outside lung(N=4) and bone lesions’ progression(N=13), of which we found that there was obvious difference in PFS ( P=0.009) between different progression groups.Toxic effects led to dose reductions, or short interruptions, or both in 20 (48.78%) of 41 patients. There were no treatment-related deaths. Conclusions: The combination of apatinib and camrelizumab obviously prolonged PFS than single apatinib in the treatment for patients with advanced osteosarcoma progressing after chemotherapy. Those with pulmonary metastatic lesions obviously had longer PFS. Whether patients benefit from overall survival needs further observation. Clinical trial information: NCT03359018.

scholarly journals RBTT-01. A PHASE 2 TRIAL WITH ABI-009 (NAB-SIROLIMUS) AS SINGLE-AGENT AND COMBINATIONS IN RECURRENT HIGH-GRADE GLIOMA (rHGG) AND IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi218-vi219 ◽  
Author(s):  
Santosh Kesari ◽  
Tiffany Juarez ◽  
Jose Carrillo ◽  
Judy Truong ◽  
Minhdan Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Mtor Inhibitors ◽  
High Grade Glioma ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Promising Target ◽  
Open Label Phase ◽  
Newly Diagnosed Glioblastoma ◽  
Cns Penetration

Abstract BACKGROUND The mTOR pathway is frequently activated in patients with GBM and is associated with reduced survival, making this pathway a promising target. However, mTOR inhibitors, including everolimus and temsirolimus, have poor brain penetration, limiting their potential use for GBM. ABI-009 is a novel albumin-bound mTOR inhibitor that has a distinct PK profile and biodistribution, including CNS penetration. The goal of this prospective, multi-cohort open-label phase 2 study is to evaluate the efficacy and safety of ABI-009 monotherapy and combination therapy in rHGG and ndGBM. METHODS Eligible patients are ≥18 years old, KPS score ≥70, and have histologically confirmed rHGG or ndGBM. Arm A has 5 cohorts in patients with rHGG, naïve to mTOR inhibitors: 1) ABI-009 single agent IV 100 mg/m2; 2–5) ABI-009 60mg/m2 plus TMZ 50mg/m2 or BEV 5mg/kg or marizomib 0.8mg/m2 or CCNU 90mg/m2. In Arm B for patients with ndGBM, ABI-009 100mg/m2 is given weekly for 4 weeks (Induction) after surgery, followed by ABI-009 at 60mg/m2 plus RT/TMZ. Up to 19 patients per cohort will be enrolled: initial 9 patients with a stopping rule that only if there are ≥2 responses will the study proceed to further enrollment of the next 10 patients (Simon’s 2-stage design). Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint for all cohorts is overall response rate per RANO criteria; secondary endpoints are median PFS and OS, 6-month and 12-month PFS, 12-month OS, and safety. This study is open and actively enrolling patients. The anticipated enrollment period is 24 months. NCT03463265

Overall response rate (ORR) in STEAM, a randomized, open-label, phase 2 trial of sequential and concurrent FOLFOXIRI-bevacizumab (BEV) vs FOLFOX-BEV for the first-line (1L) treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 492-492 ◽  
Author(s):  
Johanna C. Bendell ◽  
Benjamin R. Tan ◽  
James Andrew Reeves ◽  
Henry Xiong ◽  
Bradley G. Somer ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Tumor Location ◽  
Induction Phase ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Disease Rates ◽  
Open Label Phase ◽  
The Impact

492 Background: 3-drug chemotherapy (CT) + BEV (cFOLFOXIRI-BEV) significantly improved efficacy vs FOLFIRI-BEV for 1L mCRC tx, but safety and the impact of subsequent fluoropyrimidine-BEV maintenance tx require further definition. The phase 2 STEAM (NCT01765582) trial assessed efficacy of 1L cFOLFOXIRI-BEV vs FOLFOX-BEV and safety of alternating 2-drug CT (FOLFOX and FOLFIRI) + BEV tx monthly in a sequential sFOLFOXIRI-BEV regimen. Methods: Pts with unresectable, previously untreated mCRC were randomized 1:1:1 to BEV-containing (5 mg/kg) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks {q4w}], or FOLFOX q3w) in a 4–6 month induction phase, followed by BEV-containing maintenance tx. Stratification factors included extent of metastatic disease and tumor location. Primary objectives: 1L ORR, 1L progression-free survival (PFS), safety. Secondary objectives: resection and conversion to resectable disease rates, time to 2L PFS, overall survival. ORR was tested with a 1-sided alpha of 5%; tx arms were compared with a stratified 1-sided Cochran-Mantel-Haenszel test. PFS was analyzed descriptively. Results:Among 280 enrolled pts (median age, 57.5 yrs), 186 remainined in the study on July 1, 2015. Efficacy and safety are shown (see Table). Conclusion: While not statistically significant, there was a trend of increased ORR with cFOLFOXIRI-BEV vs FOLFOX-BEV in 1L mCRC tx. Analysis of PFS is ongoing. All 3 regimens were well tolerated. Clinical trial information: NCT01765582. [Table: see text]

scholarly journals Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial

2021 ◽  
Author(s):  
Kjetil Boye ◽  
Alessandra Longhi ◽  
Tormod Guren ◽  
Susanne Lorenz ◽  
Stine Næss ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Progression Free Survival ◽  
Complete Response ◽  
Positive Sample ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Combination Strategies ◽  
Open Label Phase ◽  
Stage 1

Abstract Aim To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. Material and methods The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Results Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2–2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8–9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. Conclusion In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 267-267
Author(s):  
Richard S. Finn ◽  
Shukui Qin ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Treatment Benefit ◽  
Recist 1.1 ◽  
Open Label Phase ◽  
Phase Iii Study

267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9071-9071
Author(s):  
Scott N. Gettinger ◽  
Rudolf M. Huber ◽  
Dong-Wan Kim ◽  
Lyudmila Bazhenova ◽  
Karin Holmskov Hansen ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Long Term Follow Up

9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text]

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4570-4570 ◽  
Author(s):  
Scott S. Tykodi ◽  
Frede Donskov ◽  
Jae-Lyun Lee ◽  
Cezary Szczylik ◽  
Jahangeer Malik ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Duration Of Response ◽  
Prior Systemic Therapy

4570 Background: KEYNOTE-427 (NCT02853344) is an open-label, single-arm, phase 2 study to evaluate efficacy and safety of first-line single-agent pembro, a programmed death 1 (PD-1) inhibitor, in patients (pts) with ccRCC (cohort A) and non–clear cell RCC (cohort B). Updated follow up from cohort A are presented. Methods: Pts with histologically confirmed ccRCC, measurable per RECIST v1.1, and no prior systemic therapy were eligible. Pts received pembro 200 mg IV Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point was objective response rate (ORR; per RECIST v1.1 blinded independent central review). Additional end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: 110 pts enrolled; median (range) follow-up was 18.0 (2.5-22.7) mo. Median age (range) was 64 (29-87); 38.2%, 47.3%, and 14.5% had favorable, intermediate, and poor IMDC risk, respectively; 47.3% were PD-L1 positive. Confirmed ORR was 36.4% with 3 (2.7%) CRs and 37 (33.6%) PRs. Median DOR was not reached. Median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was not reached. Results by IMDC category are outlined in the table. By PD-L1 status, confirmed ORR was 44.2% and 29.3% for positive and negative, respectively. By sarcomatoid differentiation (n=11), confirmed ORR was 63.6%. Treatment-related AEs occurred in 80.9%, with pruritus (28.2%) and fatigue (28.2%) most commonly reported. One pt died of treatment-related pneumonitis. Conclusions: With a median 18-months’ follow up, first-line pembro monotherapy continued to show antitumor activity in pts with ccRCC. Meaningful responses were observed in pts with intermediate/poor IMDC risk, PD-L1 positive and sarcomatoid differentiated tumors. Safety profile was comparable to previously reported. Clinical trial information: NCT02853344. [Table: see text]

scholarly journals Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression

2021 ◽  
Author(s):  
Baek-Yeol Ryoo ◽  
Ann-Li Cheng ◽  
Zhenggang Ren ◽  
Tae-You Kim ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Primary Endpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 2 ◽  
Open Label ◽  
Asian Patients ◽  
Open Label Phase ◽  
Phase 1B

Abstract Background This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). Results In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26–0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. Conclusions Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. Trial registration ClinicalTrials.gov NCT01988493.

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