PACIFIC-2: Phase 3 study of concurrent durvalumab and platinum-based chemoradiotherapy in patients with unresectable, stage III NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8573-TPS8573 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Makoto Nishio ◽  
Isamu Okamoto ◽  
Michael David Newton ◽  
Leonardo Trani ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Additional Benefit ◽  
Stage Iii ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
To Receive

TPS8573 Background: Durvalumab, a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, is approved in the US, Japan and several other countries, for the treatment of patients (pts) with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy (cCRT). These approvals were based on results from the phase 3 PACIFIC study, in which durvalumab was given 1–42 days after completion of definitive cCRT and significantly improved progression-free survival (PFS) vs placebo (median 16.8 vs 5.6 months; HR 0.52, 95% CI 0.42– 0.65; p<0.001) and overall survival (OS) vs placebo (stratified HR 0.68; 99.73% CI 0.47–0.997; p=0.0025). Increasing evidence suggests additional benefit when anti-PD-1/PD-L1 therapies are administered alongside cCRT. The PACIFIC 2 study therefore aims to assess whether durvalumab plus cCRT provides additional benefit, in terms of PFS and objective response rate (ORR), compared with cCRT alone. Methods: PACIFIC 2 is a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study. Approximately 300 pts with unresectable stage III NSCLC will be randomized (2:1) to receive either durvalumab (intravenous 1500 mg) every 4 weeks (q4w) + cCRT, or placebo q4w + cCRT. Eligible pts must have histologically or cytologically confirmed stage III disease; ECOG performance status 0 or 1; and life expectancy >12 weeks at randomization. Pts who discontinue treatment will be followed for safety and OS. Primary endpoints are PFS and ORR (RECIST v1.1) assessed via blinded independent central review. Secondary endpoints include OS; OS at month 24; complete response (CR) rate; duration of response; disease control rate; time to death/distant metastases; time from randomization to second progression; safety; and symptoms, functioning and global health status. Pts with a CR, partial response or stable disease will continue to receive durvalumab or placebo until clinical or RECIST v1.1-defined disease progression, or until another discontinuation criterion is met. Study enrollment began in March 2018 and recruitment is ongoing. Clinical trial information: NCT03519971.

Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9500-9500
Author(s):  
Alexander M. Eggermont ◽  
Andrey Meshcheryakov ◽  
Victoria Atkinson ◽  
Christian U. Blank ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Stage Iv ◽  
Median Number ◽  
Complete Resection ◽  
Stage Iii ◽  
Phase 3 ◽  
Double Blind ◽  
Grade 3 ◽  
To Receive

9500 Background: The phase 3 double-blind EORTC 1325/KEYNOTE-054 trial evaluated pembrolizumab (pembro) vs placebo in stage III cutaneous melanoma patients (pts) with complete resection of lymph nodes. Pembro improved RFS (hazard ratio [HR] 0.57) and DMFS (HR 0.60) (Eggermont, NEJM 2018, TLO 2021). In the pembro group, the incidence of immune related AE (irAE) grade 1-5 was 37%, and of grade 3-5 was 7%. We present the safety profile, response rate and PFS for the subset of pts who had a recurrence and crossed over or were rechallenged with pembrolizumab, within protocol. Methods: Pts were randomized to receive iv. pembro 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year). Upon recurrence with no brain metastases, pts with an ECOG PS 0-2 were eligible to enter part 2 of the study, i.e. to receive pembro 200 mg iv. every 3 weeks for a maximum of 2 years, for crossover (those who received placebo) or rechallenge (those who recurred ≥6 months after completing one year of pembro therapy). Treatment was stopped in case of disease progression (RECIST 1.1) or unacceptable toxicity. Results: At the clinical cut-off (16-Oct-2020), 298 (59%) pts had a disease recurrence in the placebo group; 155 pts participated in the crossover part 2 of the trial. A total of 297 (58%) pts completed the 1-yr pembro adjuvant treatment, of whom 47 had a recurrence ≥6 mths from the stop of treatment and 20 entered in the rechallenge part of the trial. Among 175 pts who started pembro in Part 2, 160 discontinued due to completion of therapy (N=24), disease progression (N=88), toxicity (N=20), investigator's decision (N=21), or other reason (N=7); 15 pts were still on-treatment. Results for the 2 groups are provided in the table. The median number of doses was 12 and 5.5, respectively (resp), and the median follow-up was 41 and 19 mts, resp. Among the 175 pts, 51 (29%) had a grade 1-4 irAE (by group: 47 [30%] and 4 [20%] resp) and 11 (6%) a grade 3-4 irAE. Conclusions: Pembrolizumab treatment after crossover yielded a 39% ORR in evaluable pts and an overall 3-yr PFS of ̃32%, but after rechallenge the efficacy was lower. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA The median PFS (95% CI) from start of Part 2 was 14 (5-27) and 8 (5-15) mts for stage III-resected and III/IV various, resp. Among the 80 stage IV crossover pts with evaluable disease, 31 (39%) had an objective response: 14 (18%) CR, 17 (21%) PR. The 2-yr PFS rate from response was 69% (95% CI 48-83%). For these 80 pts, the median PFS was 6.1 mts and the 3-yr PFS rate was 31% (95% CI 21-41%). Among 9 stage IV rechallenged pts with an evaluable disease, 1 (11%) reached CR, 3 had SD and 5 PD. Clinical trial information: NCT02362594. [Table: see text]

Gemstone-301: A phase III clinical trial of CS1001 as consolidation therapy in subjects with locally advanced/unresectable (stage III) non-small cell lung cancer (NSCLC) who have not progressed after prior concurrent/sequential chemoradiotherapy (CRT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8572-TPS8572
Author(s):  
Yi-Long Wu ◽  
Ming Chen ◽  
Qing Zhou ◽  
Hao Li ◽  
Wenyi Sun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Transgenic Rat ◽  
Consolidation Therapy ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

TPS8572 Background: In China, the standard of care for patients with unresectable Stage III NSCLC is platinum-based doublet chemotherapy given concurrently or sequentially with radiotherapy. However, the median progression-free survival (PFS) of those patients is poor (approximately 8-10 months) and 5-year overall survival (OS) rate is only 15%. Recently, treatment with durvalumab resulted in significantly longer PFS and OS than placebo for patients with locally advanced/unresectable NSCLC whose disease did not progress after definitive concurrent chemoradiotherapy (cCRT) in PACIFC trial. CS1001 is the first full-length, fully human programmed death ligand-1 (PD-L1) targeted immunoglobin G4 (IgG4, s228p) monoclonal antibody (mAb) developed by the OMT transgenic rat platform. The Phase Ia/Ib study (GEMSTONE-101, NCT03312842) demonstrated that CS1001 was well tolerated and had promising anti-tumor activities across a range of tumors including NSCLC. GEMSTONE-301 is a randomized, double-blind, Phase III study to compare the efficacy and safety of CS1001 versus placebo as consolidation therapy in Stage III unresectable NSCLC patients. This is the first Phase III trial on an anti-PD-(L)1 mAb initiated in China for this indication. Methods: In this trial, eligible patients with locally advanced/unresectable (Stage III) NSCLC who have not progressed after prior concurrent/sequential CRT are 2:1 randomized to receive CS1001 1200 mg, every 3 weeks or placebo, every 3 weeks. Stratification factors for randomization include ECOG status (0 versus 1), chemoradiotherapy (concurrent versus sequential) and total radiotherapy dose ( < 60 Gy versus ≥ 60 Gy). Study treatment will be given for up to 24 months or until disease progression, intolerable toxicity, consent withdrawal, or discontinuation for other reason. Tumor assessments will be performed every 9 weeks in the first year and every 12 weeks thereafter by RECIST v1.1. AEs will be monitored throughout the study and graded according to NCI-CTCAE v4.03. Primary endpoint is PFS evaluated by investigators according to RECIST v1.1. Secondary endpoints are PFS evaluated by Blinded Independent Center Review (BICR), objective response rate, OS, time to death/distant metastasis (TTDM), safety and pharmacokinetics (PK) profile. Enrollment is ongoing across sites in China and will continue until 402 patients are randomized. Clinical trial information: NCT03728556.

Thoracic radiotherapy PLUS durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy: Employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy—The TRADE-hypo trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8585-TPS8585
Author(s):  
Farastuk Bozorgmehr ◽  
Jessica Juergens ◽  
Michaela Hammer-Hellmig ◽  
Christian Meyer Zum Bueschenfelde ◽  
Johannes Classen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response ◽  
Stage Iii ◽  
Hypofractionated Radiotherapy ◽  
Poor Performance Status ◽  
Thoracic Radiotherapy ◽  
Therapy Algorithm ◽  
Safety And Efficacy ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

TPS8585 Background: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide highlighting the importance of improving current therapeutic options. In particular, elderly and frail patients are not only underrepresented in clinical trials, but also frequently do not receive standard treatment regimens due to comorbidities. For example, patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) do not benefit from the recent seminal therapy algorithm change for this disease, i.e. consolidation therapy with the immune checkpoint inhibitor (ICI) durvalumab after combined radiochemotherapy (RChT). Instead, these patients are treated with radiotherapy only, raising the serious concern of undertreatment. This issue is addressed by the TRADE-hypo clinical trial that investigates a novel therapy option for NSCLC stage III patients not capable of receiving CHT. To this end, thoracic radiotherapy (TRT) is administered together with durvalumab, employing the synergism created by the combination of restoring anti-tumor immune response by the ICI with the induction of immunogenicity by irradiation. The latter effect has been suggested to be further boosted by hypofractionated radiotherapy, which could also be more practicable for the patient. Taken these considerations into account, the TRADE-hypo trial addresses safety and efficacy of durvalumab therapy combined with either conventional or hypofractionated TRT. Methods: The TRADE-hypo trial is a prospective, randomized, open-label, multicentric phase II trial. Eligible patients are diagnosed with unresectable stage III NSCLC and not capable of receiving sequential RChT due to high vulnerability as reflected by a poor performance status (ECOG 2 or ECOG1 and CCI≥ 1) and/or high age (≥ 70)]. Two treatment groups are evaluated: Both receive durvalumab (1,5000 mg, Q4W) for up to 12 months. In the CON-group this is combined with conventionally fractionated TRT (30 x 2 Gy), while in the HYPO-group patients are treated with hypofractionated TRT (20 x 2.75 Gy). In the HYPO-arm, a safety stop-and-go lead-in phase precedes full enrollment. Here, patients are closely monitored with regard to toxicity (i.e., pneumonitis grade ≥ 3 within 8 weeks after TRT) in small cohorts of 6. The primary objective of the trial is safety and tolerability. As a primary efficacy endpoint, the objective response rate after 3 months will be evaluated. Further endpoints are additional parameters of safety and efficacy, as well as the comprehensive collection of biomaterials to be analyzed regarding treatment-induced changes and potential novel biomarkers. As of February 10, 2021, 9 patients of planned 88 patients have been enrolled in the TRADE-hypo trial. Clinical trial information: NCT04351256.

Induction (ICT) or consolidation chemotherapy (CT) with cisplatin (C) and paclitaxel (P) plus concurrent chemo-radiation (CT/TRT) with cisplatin and vinorelbine (V) for unresectable non-small cell lung cancer (NSCLC) patients (pts): Randomized phase II trial GFPC-GLOT-IFCT 02–01

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7048-7048 ◽  
Author(s):  
P. Fournel ◽  
A. Vergnenégre ◽  
G. Robinet ◽  
H. Léna ◽  
R. Gervais ◽  
...  
Keyword(s):  
Response Rate ◽  
Superior Vena ◽  
Objective Response ◽  
Vena Cava ◽  
Primary Objective ◽  
Stage Iii ◽  
Massive Hemoptysis ◽  
Unresectable Stage ◽  
End Of Treatment ◽  
Stage Iii Nsclc

7048 Background: Concurrent CT/TRT is the standard treatment for unresectable stage III NSCLC, but the optimal sequencing of TRT and CT is not well defined.Consolidation CT with taxane seems to be a good approach (SWOG 95–04). Methods: Unresectable stage III NSCLC pts (weight loss < 10%, ECOG PS 0–1, no supraclavicular lymph node or superior vena cava syndrome) were eligible. in Arm A, pts received 2 cycles of C 80 mg/m2 and P 200 mg/m2 followed by a concurrent CT/TRT including TRT as 66 Gy in 33 fractions and C 80 mg/m2 d1,29 and 57 and V d1,8,29,36,57 and 64. In Arm B, the same CT/TRT began on d1 followed by 2 cycles of C and P. The primary objective was response rate at the end of treatment, assessed by RECIST criteria. 132 pts were needed. Results: From 05/2002 to 03/2005, 133 pts were included by 35 centers. 5 pts were ineligible. Both groups were well-matched for baseline characteristics. 30 pts were stage IIIAN2 and 98 stage IIIB. Toxicities (106 pts analyzable) grade 3–4 by CTC and RTOG criteria (Arm A/Arm B) were: neutropenia 36%/41%, infection 11%/15%, esophagitis 6%/13%, pneumonitis 0%/1%. 5 toxic deaths were observed (2 sepsis, 1 massive hemoptysis, 1 post-irradiation pneumonitis, 1 esophageal fistula). In Arm A, objective response rate was 36% after ICT. At the end of treatment, response rate (Arm A/Arm B) was in intent to treat: progression 19%/19%, stable-disease 6%/11%, objective response 55%/48%. 13 pts were not evaluable for response in Arm A and 14 in Arm B [ table ]. Conclusions: Toxicities and response rates are similar in both arms, but ICT followed by CT/TRT appears to provide a better therapeutic outcome. [Table: see text] No significant financial relationships to disclose.

A phase III study of Æ-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell lung cancer (NSCLC) (NCI T99–0046, RTOG 02–70, MDA 99–303)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7527-7527 ◽  
Author(s):  
C. Lu ◽  
J. J. Lee ◽  
R. Komaki ◽  
R. S. Herbst ◽  
W. K. Evans ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Stage Iii ◽  
Type I ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Significant Difference ◽  
Stage Iii Nsclc

7527 Background: Æ-941 is a shark cartilage extract with antiangiogenic properties. We conducted a placebo-controlled trial testing Æ-941, with IC and CRT, in unresectable stage III NSCLC. Methods: Eligibility criteria included performance status (PS) < 2, weight loss < 10%. Subjects received one of two treatment regimens depending on site of enrollment: carboplatin (C) (AUC 6) and paclitaxel (P) (200 mg/m2) × 2 cycles followed by CRT (60 Gy/30 fractions) with weekly C (AUC 2) and P (45 mg/m2) × 6 doses or cisplatin (CDDP) (75 mg/m2, d1) and vinorelbine (V) (30 mg/m2, d1 and 8) × 2 cycles followed by CRT (60 Gy/30 fractions) with CDDP (75 mg/m2, day 1) and V (15 mg/m2, d1 and 8) × 2 cycles. Subjects were randomized to receive Æ-941 (Arm A) or placebo (Arm B), 120 mL orally twice daily, at the start of IC and continuing after CRT as maintenance therapy. Randomization was stratified for stage, gender, and type of chemotherapy. The primary endpoint was overall survival (OS), with a planned sample size of 756 subjects providing 80% power to detect a 25% difference in OS, assuming a control arm median survival time (MST) of 13 months, type I error 0.05. Results: Between 6/00 and 2/06, 384 subjects were enrolled onto the trial and randomized. In 2/06 the trial was closed to new patient entry due to insufficient accrual. This final analysis is based on 379 randomized and eligible subjects (188 arm A, 191 arm B). Subject characteristics: 60% male, median age 63 years (range 37–84), 56% stage IIIB, 58% C-based chemotherapy, median follow-up 3.7 years. There was no significant difference in OS between arms A and B, with MSTs of 14.4 (95% CI 12.6–17.9) and 15.6 (95% CI 13.8–18.1) months, respectively (log-rank p=0.73). OS by pre-specified stratification factors: stage IIIB vs IIIA (MST 13.9 vs. 17.4 months, p=0.25), C vs. CDDP chemotherapy (MST 14.4 vs. 16.7 months, p=0.13), and male vs. female (MST 15.7 vs. 15.1 months, p=0.74). The study drug was well tolerated. Fewer subjects in arm A experienced grade 3 or higher adverse events (66% vs. 77%, p=0.018). Conclusions: The addition of Æ−941 to IC and CRT does not improve OS in patients with unresectable stage III NSCLC. No significant financial relationships to disclose.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

START: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Charles Andrew Butts ◽  
Mark A. Socinski ◽  
Paul Mitchell ◽  
Nick Thatcher ◽  
Libor Havel ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Phase Iii ◽  
Stage Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Double Blind ◽  
Unresectable Stage ◽  
Clinical Hold ◽  
Stage Iii Nsclc ◽  
Symptom Progression

7500 Background: L-BLP25 is a MUC1 antigen specific cancer immunotherapy. We report results from the phase III START study of L-BLP25 in patients (pts) not progressing after primary chemoradiotherapy (CRT) for stage III NSCLC. Methods: From Jan 2007 to Nov 2011, 1513 pts with unresectable stage III NSCLC that did not progress after CRT (platinum based chemo and ≥50 Gy) were randomized (2:1; double-blind) to L-BLP25 (806 µg lipopeptide) or placebo (PBO) SC weekly x 8 then Q6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m2 x 1 or saline was given 3 days prior to first L-BLP25/PBO dose. Primary endpoint was overall survival (OS). Results: The primary analysis population (n=1239) was defined prospectively to try to account for a clinical hold by excluding pts randomized 6 months (m) before the hold. Arms were balanced for baseline characteristics. Median age was 61 y; 38.2% had stage IIIA and 61.3% IIIB; 65% had concurrent and 35% sequential CRT. Median OS was 25.6 m with L-BLP25 vs. 22.3 m with PBO (adjusted HR 0.88, 95% CI 0.75-1.03, p=0.123). Secondary endpoints time-to-progression and time-to-symptom-progression support consistency of results: HR 0.87 (95% CI 0.75-1.00, p=0.053) and 0.85 (95% CI 0.73-0.98, p=0.023). In predefined subgroup analyses, pts with concurrent CRT (n=806) had median OS of 30.8 m (L-BLP25) vs. 20.6 m (PBO; HR 0.78, 95% CI 0.64-0.95, p=0.016), while median OS with sequential CRT was 19.4 m (L-BLP25) vs. 24.6 m (PBO; HR 1.12, 95% CI 0.87-1.44, p=0.38; interaction p=0.032, Cox PH model). Sensitivity analyses revealed that there was no OS benefit in pts randomized 6 m before the hold (HR 1.09, CI 0.75-1.56, p=0.663). LEBLP25 was well tolerated with no safety concerns identified and no emergent evidence of immune related adverse events. Conclusions: L-BLP25 maintenance therapy in stage III NSCLC was well tolerated, but did not significantly prolong OS. Sensitivity analyses showed a smaller treatment effect due to the clinical hold, suggesting that longer uninterrupted treatment with L-BLP25 is required. Clinically meaningful prolongation of OS was observed in the predefined subgroup of pts with primary concurrent CRT. Clinical trial information: NCT00409188.

ARASENS: A phase 3 trial of darolutamide in combination with docetaxel for men with metastatic hormone-sensitive prostate cancer (mHSPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS383-TPS383 ◽  
Author(s):  
Matthew Raymond Smith ◽  
Fred Saad ◽  
Maha Hussain ◽  
Cora N. Sternberg ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase 1 ◽  
Performance Status ◽  
Physical Symptoms ◽  
Castration Resistant Prostate Cancer ◽  
Opioid Use ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Disease Extent

TPS383 Background: The addition of either docetaxel or abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improves overall survival (OS) compared with ADT alone in men with mHSPC. It is hypothesized that other androgen receptor (AR)-targeted therapies could be combined with docetaxel for mHSPC. Darolutamide (ODM-201) is an investigational oral AR antagonist with a unique chemical structure and negligible blood-brain barrier penetration that inhibits tumor growth by binding to AR and AR mutants (eg, W742L and F877L) with high affinity and specificity. In phase 1/2 ARADES and phase 1 ARAFOR trials, darolutamide demonstrated antitumor activity and was well tolerated in men with metastatic castration-resistant prostate cancer (mCRPC). ARASENS will evaluate the addition of darolutamide to standard ADT and docetaxel in men with mHSPC. Methods: This international, randomized, double-blind, placebo-controlled phase 3 trial (NCT02799602) is being conducted at > 300 sites in 23 countries. ~1300 men with newly diagnosed mHSPC will be randomized 1:1 to darolutamide (600 mg orally twice daily) or matching placebo. All patients will receive standard ADT + docetaxel (6 cycles). Patients will be stratified by disease extent and alkaline phosphatase level. Key inclusion criteria: histologically or cytologically confirmed PC with documented metastases, started ADT ± first-generation antiandrogen therapy ≤12 weeks before randomization, and ECOG performance status 0-1. The primary end point is OS. Secondary end points include time to mCRPC, initiation of subsequent anticancer therapy, symptomatic skeletal event (SSE)-free survival, time to first SSE, first opioid use, pain progression, and worsening of physical symptoms. Safety will be assessed. ARASENS is actively enrolling at > 280 sites across 23 countries. Clinical trial information: NCT02799602.

Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6589-TPS6589 ◽  
Author(s):  
Lillian L. Siu ◽  
Barbara Burtness ◽  
Ezra E.W. Cohen ◽  
Kevin Joseph Harrington ◽  
Lisa F. Licitra ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Imaging ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor ◽  
End Points

TPS6589 Background: The PD-1 inhibitor pembrolizumab is currently approved as first-line monotherapy for patients with R/M HNSCC whose tumors express PD-L1 combined positive score (CPS) ≥1. In a phase 1b/2 trial (NCT02501096) of pembrolizumab plus lenvatinib (multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT) in solid tumors, the combination demonstrated promising antitumor activity and a manageable safety profile in patients with HNSCC. LEAP-010 (NCT04199104) is a randomized, double-blind, placebo-controlled, phase 3 study that will evaluate the efficacy and safety of first-line pembrolizumab with or without lenvatinib in patients with PD-L1–positive R/M HNSCC. Methods: Key eligibility criteria include histologically confirmed R/M HNSCC incurable by local therapies, PD-L1–positive tumor (CPS ≥1) as determined by central laboratory, measurable disease as assessed by blinded independent central review (BICR) per RECIST v1.1, and ECOG performance status (PS) 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab plus lenvatinib or pembrolizumab plus placebo. Randomization will be stratified by PD-L1 status defined by tumor proportion score ( < 50% vs ≥50%), human papillomavirus status for oropharynx cancer (positive vs negative), and ECOG PS (0 or 1). Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles (~2 years) and oral lenvatinib 20 mg or placebo once daily; patients may continue to receive lenvatinib or placebo after pembrolizumab treatment is complete. Treatment will continue until BICR-verified disease progression or unacceptable toxicity. Pembrolizumab retreatment (second course) for 17 additional cycles will be allowed for eligible patients who stop pembrolizumab and subsequently experience BICR-verified disease progression. These patients could have stopped treatment with stable disease, partial response, or complete response or after 35 cycles of pembrolizumab for reasons other than disease progression or toxicity. Tumor imaging assessment will be performed at week 6, then every 6 weeks until 1 year, and thereafter every 9 weeks. Primary end points are objective response rate and progression-free survival, assessed by BICR per RECIST v1.1, and overall survival. Secondary end points are duration of response and safety and tolerability. Recruitment is ongoing; planned enrollment is ~500 patients. Clinical trial information: NCT04199104 .

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