Brigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20503-e20503 ◽  
Author(s):  
Myung-Ju Ahn ◽  
D. Ross Camidge ◽  
Marcello Tiseo ◽  
Karen L. Reckamp ◽  
Karin Holmskov Hansen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase 1 ◽  
Objective Response ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Best Response ◽  
Grade 3 ◽  
Nsclc Patients ◽  
To Receive ◽  
Randomized Phase 2

e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text]

Phase I/II study of MKC-1 and pemetrexed (PEM) as second-line therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19005-e19005
Author(s):  
N. H. Hanna ◽  
D. Estes ◽  
J. Arnott ◽  
S. Marcotte ◽  
A. Hannah ◽  
...  
Keyword(s):  
Phase 1 ◽  
Combined Treatment ◽  
Single Agent ◽  
Second Line ◽  
Phase 2 ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Grade 3 ◽  
One Year

e19005 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity against NSCLC cell lines including multi-drug resistant lines, and single agent activity in NSCLC pts. Binding targets of MKC-1 include microtubules, members of the importin-β family and AKT-mTOR. This phase 1/2 study evaluated MKC-1 in combination with PEM as second-line therapy in pts with advanced NSCLC. Methods: Eligible pts had NSCLC previously treated with one regimen for metastatic disease or disease progression within one year following adjuvant and neoadjuvant therapy. Phase 1 dose escalation used 3+3 design. Phase 2 pts were treated with MKC-1 at 75 mg/m2 given p.o. BID for 14 days along with PEM at 500 mg/m2 given i.v. on day 1 of each 21 day cycle. Following 4 cycles of combined treatment, single agent MKC-1 was continued as maintenance therapy. An interim analysis after 17 pts in phase 2 would allow accrual to continue provided one response was confirmed. Results: 27 pts were enrolled (8 in phase 1 and 19 in phase 2). Median age/PS for phase 2 is 64/1 and 89% had adenocarcinoma. Total # of treatment cycles to date for phase 2 pts is 95, with a median of 4 cycles. Of the 19 phase 2 pts, 18 were evaluable for tumor response. The best response was confirmed PR, noted in 3 pts. 5 additional pts (4 confirmed) had minor responses (>10% but <30% shrinkage). One additional pt continues on study with stable disease for >18 months. In phase 2 (n=19), all grade toxicities were anorexia (59%), fatigue (63%), nausea (58%), and dyspnea (48%). Grade 3/4 toxicities included fatigue (26%); neutropenia (22%); dyspnea, anorexia, AST and ALT elevation (11% each); nausea and constipation (5% each). 7 pts had at least one dose reduction of both PEM and MKC-1 and 3 additional pts had only MKC-1 reduced. Median PFS was 86 days with two pts continuing on study (treated for 530+ days and 140+ days, respectively). Conclusions: The phase 2 dose of MKC-1 (75 mg/m2 BID) and PEM (500 mg/m2) has been defined. The combination is well tolerated with 17% of patients achieving a confirmed PR thus far. A decision to proceed with additional accrual in this single arm study versus initiating a randomized phase 2 study of this combination is pending. [Table: see text]

Oral weekly MLN9708, an investigational proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma (MM): A phase I/II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8033-8033 ◽  
Author(s):  
Paul Gerard Guy Richardson ◽  
Jesus G. Berdeja ◽  
Ruben Niesvizky ◽  
Sagar Lonial ◽  
Vivek Roy ◽  
...  
Keyword(s):  
Proteasome Inhibitor ◽  
Phase 1 ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Phase 2 ◽  
Nonhematologic Toxicity ◽  
Immunomodulatory Drug ◽  
Grade 3 ◽  
To Receive

8033 Background: MLN9708 is an oral, reversible 20S proteasome inhibitor. The feasibility of combining a proteasome inhibitor with an immunomodulatory drug and a steroid in previously untreated MM has been demonstrated with the RVD regimen. This is the first study of MLN9708 in combination with lenalidomide and dexamethasone (NCT01217957). Here we report the phase (Ph) 1 MTD and preliminary Ph 2 results. Methods: Pts with previously untreated MM, aged ≥18 yrs with measurable disease received oral MLN9708 (phase 1: 1.68–3.95 mg/m2) days 1, 8, and 15, lenalidomide 25 mg days 1–21, and dexamethasone 40 mg days 1, 8, 15, and 22, for up to twelve 28-day cycles. Primary objectives were determination of safety, MTD, and recommended phase 2 dose (RP2D) (Ph 1), and CR+VGPR rate (Ph 2). Results: At data cut-off (Dec 1, 2011), 29 pts had been enrolled (15 Ph 1, 14 Ph 2). Median age was 64 yrs (range 40–82); 69% ISS stage II/III. In Ph 1, the MLN9708 MTD was determined as 2.97 mg/m2 and the RP2D as 2.23 mg/m2; for Ph 2, the RP2D was converted to a 4.0 mg fixed dose based on population PK results. Ph 1 pts have received a median of 6 treatment cycles (range 1–11), 8 received ≥6 cycles; 6 stopped to receive ASCT, 7 are ongoing. Ph 2 pts received a median of 1 (range 1–2), all are ongoing. Grade ≥3 hematologic toxicity was reversible and included anemia (n=2) and thrombocytopenia (n=1). Grade ≥3 nonhematologic toxicity included erythematous rash, syncope, and vomiting (2 pts each). All-grade drug-related peripheral neuropathy was seen in 6 pts (21%), including grade 2 with pain in 2 (both Ph 1 at doses above the MTD). Two pts discontinued due to AE; there were 5 pts who had serious drug-related AE (all Ph 1). Of 19 response-evaluable pts (Ph 1 + Ph 2), all achieved ≥PR, including 5 CR (1 sCR), 4 VGPR, and 10 PR; all remain in response with duration of confirmed response of up to 9.5 months. Of 4 response-evaluable Ph 2 pts, 1 has achieved VGPR and 3 PR to date. Conclusions: Oral MLN9708 plus lenalidomide and dexamethasone appears well tolerated with manageable toxicity. These data show antitumor activity at the RP2D in pts with previously untreated MM, with ≥PR in all pts to date.

SYNFRIZZ: A first-in-human (FIH) study of a radiolabeled monoclonal antibody (Mab) targeting frizzled homolog 10 (FZD10) in patients (pts) with advanced synovial sarcomas (SyS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11054-11054
Author(s):  
Philippe Alexandre Cassier ◽  
Anne Laure Giraudet ◽  
Chicaco Iwao-Fukukawa ◽  
Gwenaelle Garin ◽  
Jean-Noel Badel ◽  
...  
Keyword(s):  
Objective Response ◽  
Tumor Uptake ◽  
Best Response ◽  
Primary Endpoints ◽  
Clinical Investigations ◽  
Common Grade ◽  
Synovial Sarcomas ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

11054 Background: Advanced SyS are rare tumors with limited curative options. FZD10 is highly expressed in SyS but not in normal adult tissue. OTSA101 is a MAb targeting FZD10, labelled with a radioisotope. Methods: We conducted a phase I, FIH study including adult pts with advanced, refractory SyS. In part 1, pts received OTSA101 labelled with In111 used as radiotracer to assess biodistribution and tumor uptake. In part 2, pts with significant tumor uptake were randomized to receive OTSA101 labelled with 370MBq of Y90 (Arm A) or 1110MBq Y90 (Arm B). Primary endpoints were occurrence of unacceptable biodistribution /lack of tumor uptake in part 1 and occurrence of related adverse events (AEs) Grade ≥ 3 during the first 8 weeks following injection of Y90OTSA101 in part 2. Responses were assessed per RECIST 1.1. Results: From January 2012 to June 2015, 20 pts (10 females, median age 43, range 21-67) with advanced SyS were enrolled. Ten pts (50%) had sufficient tumor uptake to proceed to part 2 and 8 were randomized (Arm A: 3 and Arm B: 5). Two pts were not randomized due to worsening PS. During part 2, the most common Grade ≥ 3 AEs were haematological, including reversible lymphopenia, thrombocytopenia and neutropenia, and were more common in Arm B. One pt with SD after 12 weeks received a 2nd injection of 90Y-OTSA101, but experienced fatal hemoptysis. No objective response was observed. Best response was SD in 5/8 pts lasting up to 21 weeks for 1 pt. Conclusions: This FIH shows that radioimmunotherapy targeting FZD10 is feasible and safe in SyS pts. Tumor uptake was heterogeneous but sufficient to select 50% of pts for 90Y-OTSA101 treatment. Due to limited sample size, further clinical investigations are needed to assess the therapeutic activity of 90Y-OTSA101 with a recommended dose of 1110MBq of 90Y. Clinical trial information: NCT01469975.

A randomized phase 2 study of durvalumab monotherapy and in combination with tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): ALPS study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 217-217 ◽  
Author(s):  
Eileen Mary O'Reilly ◽  
Do-Youn Oh ◽  
Neesha Dhani ◽  
Daniel John Renouf ◽  
Myung Ah Lee ◽  
...  
Keyword(s):  
Objective Response ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Controlled Study ◽  
Phase 2 ◽  
Intrinsic Resistance ◽  
Multiple Cancer ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Randomized Phase 2

217 Background: Durvalumab (D) and tremelimumab (T), monoclonal antibodies against PD-L1 and CTLA-4 immune checkpoints, have shown efficacy as monotherapy/combination therapy in multiple cancer types. Herein, we report a randomized phase 2 study to evaluate efficacy and safety of D monotherapy with or without T (D+T) in previously treated mPDAC. Methods: Part A was a lead-in safety and signal-seeking study with plans to expand to Part B as a nonrandomized or randomized controlled study pending efficacy signal. Eligible pts had progressive disease (PD) following front-line 5-FU- or gemcitabine-based therapy. In Part A, pts were randomized to D (1.5 g IV Q4W) or D+T (D 1.5 g IV + T 75 mg IV Q4W × 4 doses → D 1.5 g IV Q4W) for up to 12 months (mo) or until confirmed PD or unacceptable toxicity. Primary endpoint was investigator-assessed objective response rate per RECIST 1.1. Results: In Part A, 65 pts were randomized to D (n = 33) or D+T (n = 32). Due to a pretreatment death, 64 pts received therapy. Eleven pts (34.4%) in D+T and 10 (31.3%) in D had treatment-related adverse events (trAEs); 7 (22%) in D+T and 2 (6%) in D had grade ≥3 trAEs. Common trAEs: fatigue (12.5%), diarrhea (12.5%), and hypothyroidism (9.4%) in D+T; fatigue (9.4%), diarrhea (6.3%), and pruritus (6.3%) in D. Grade ≥3 trAEs were diarrhea (9.4%), fatigue (6.3%) in D+T and ascites (3.1%), hepatitis (3.1%), and increased lipase (3.1%) in D. In D+T, 3 (9.4%) pts and 1 (3.1%) in D discontinued therapy due to trAEs. No trAEs resulted in death. In D+T, 1 (3.1%) pt had a durable confirmed partial response (PR) > 12 mo and disease control rate (DCR) was 9.4%. In D, 2 (6.1%) pts had unconfirmed PRs, and the DCR was 6.1%. Median PFS in both arms was 1.5 mo, and median OS was 3.1 mo in D+T and 3.6 mo in D. Biomarker analyses (tumor mutation burden, PD-L1 and microsatellite status) are currently being evaluated. Conclusions: Typical safety profiles were observed for D or D+T in mPDAC. Part B was not enrolled as the threshold for efficacy was not met in Part A. D and D+T had modest activity in second-line non-selected mPDAC, underpinning the need for multimodal immune-based combinations to overcome intrinsic resistance in this disease. Clinical trial information: NCT02558894.

Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
Michael Robert Migden ◽  
Nikhil I. Khushalani ◽  
Anne Lynn S. Chang ◽  
Danny Rischin ◽  
Chrysalyne D. Schmults ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Median Duration ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase 2 ◽  
Primary Analysis ◽  
Curative Surgery ◽  
Grade 3

6015 Background: Cemiplimab (REGN2810) produced substantial antitumor activity with durable responses in Phase 1 CSCC expansion cohorts and Phase 2 metastatic (m) CSCC cohort. We now present the primary analysis of the Phase 2 laCSCC cohort (NCT02760498; data cutoff date: Oct 10, 2018). Methods: Pts with laCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 78 pts were enrolled (59 M/ 19 F; median age: 74 years; ECOG PS: 0 in 38 pts, 1 in 40 pts; primary CSCC site: head/neck in 79.5%; prior systemic therapy: 15.4%; prior radiotherapy: 55.1%). Median duration of follow-up was 9.3 months (range: 0.8–27.9). ORR by central review was 43.6% (95% CI: 32.4–55.3; 10 CRs and 24 PRs); investigator-assessed (INV) ORR was 52.6% (95% CI: 40.9–64.0; 13 CRs and 28 PRs). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 24.2 months and was still ongoing. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.8% (95% CI: 51.1–73.5). Median observed time to response was 1.9 months (range: 1.8–8.8). Median progression-free and overall survival have not been reached. Tumor PD-L1 status is available for 48/78 pts, tumor mutational burden analysis (from targeted exome panel) is ongoing for ≥40/78 pts; response correlation analyses are planned. The most common treatment-emergent adverse events (AEs; all grades, Grade ≥3) were fatigue (42.3%, 1.3%), diarrhea and pruritus (both 26.9%, 0%), and nausea (21.8%, 0%). INV grade ≥3 immune-related AEs occurred in 10.3% of pts. One pt died due to an unknown cause that was assessed as treatment-related. Conclusions: Cemiplimab 3 mg/kg Q2W showed substantial antitumor activity, durable responses, and acceptable safety profile in pts with laCSCC. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.

FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
Antoine Hollebecque ◽  
Juan W. Valle ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Gene Fusions ◽  
Phase 2 ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy ◽  
Grade 3

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.

Phase I/II study of sunitinib malate in combination with gefitinib in patients (pts) with metastatic renal cell carcinoma (mRCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5097-5097 ◽  
Author(s):  
P. H. Patel ◽  
G. V. Kondagunta ◽  
B. G. Redman ◽  
G. R. Hudes ◽  
S. T. Kim ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Ejection Fraction ◽  
Dose Level ◽  
Egf Receptor ◽  
Phase 1 ◽  
Objective Response ◽  
Cytokine Therapy ◽  
Phase 2 ◽  
Sunitinib Malate ◽  
Grade 3

5097 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGF- and PDGF- receptors with substantial antitumor activity against mRCC (JAMA 2006;295:2516). This study was conducted to evaluate the safety and efficacy of sunitinib in combination with gefitinib, an EGF-receptor inhibitor. Methods: Eligibility included mRCC with clear cell component. The phase 1 part of the study was conducted to determine the maximum tolerated dose (MTD) of sunitinib in combination with gefitinib, and subsequently pts were enrolled in the phase 2 part to further evaluate safety and antitumor activity. Pts were treated with sunitinib at assigned dose level (37.5 mg or 50 mg) orally daily for 4 weeks on, followed by 2 weeks off (Schedule 4/2) and gefitinib at 250 mg daily. The primary endpoint for the phase 2 part of the study was objective response according to RECIST. Results: Forty-two pts were enrolled; 11 pts in phase 1 and 31 pts in phase 2. Median age was 65 years (range: 29–78) and 35 pts (83%) had =2 metastatic sites. Twenty-eight pts (67%) had prior cytokine therapy, 11 pts (26%) had no prior cytokine therapy, and 3 pts (7%) received prior vaccine therapy. Two dose limiting toxicities (DLTs) were observed at the 50-mg dose level (grade 3 fatigue and grade 2 ejection fraction decline), and 37.5 mg on Schedule 4/2 in combination with gefitinib 250 mg daily was determined to be the MTD. The median duration on treatment was 8.3 months for phase 1. Thirty-six pts are evaluable for response and 6 are too early. Eleven pts (30%) achieved a partial response and 15 pts (42%) stable disease. The most common grade 3 treatment-related adverse events observed in phase 1 were diarrhea and nausea (n=2) and for phase 2 were diarrhea (10%) and gastrointestinal hemorrhage (6%). Two pts from phase 2 were withdrawn from the study due to treatment-related adverse event; ejection fraction decline and cardiac arrhythmia, both of which were reversible after treatment discontinuation. Conclusions: The study established dose and feasibility for sunitinib in combination with gefitinib. Early evaluation of the data suggests tolerability for the combination and relative efficacy data compared to sunitinib monotherapy will be assessed with longer patient follow-up. No significant financial relationships to disclose.

A randomized phase 2 trial of MM-121, a fully human monoclonal antibody targeting ErbB3, in combination with erlotinib in EGFR wild-type NSCLC patients.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 8051-8051 ◽  
Author(s):  
Lecia V. Sequist ◽  
Ariel Lopez-Chavez ◽  
Robert Charles Doebele ◽  
Jhanelle Elaine Gray ◽  
Wael A. Harb ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Human Monoclonal Antibody ◽  
Phase 2 ◽  
Wild Type ◽  
Phase 2 Trial ◽  
Antibody Targeting ◽  
Nsclc Patients ◽  
Randomized Phase 2

Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20502-e20502 ◽  
Author(s):  
Sai-Hong Ignatius Ou ◽  
Marcello Tiseo ◽  
D. Ross Camidge ◽  
Myung-Ju Ahn ◽  
Rudolf M. Huber ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Review Committee ◽  
Small Cell Lung ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
A Site ◽  
To Receive ◽  
Clinical Trial Information

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]

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