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  • / Gemcitabine (Gem) and nab-paclitaxel (NP) ± nivolumab (nivo) ± CD40 agonistic monoclonal antibody APX005M (Sotigalimab), in patients (Pts) with untreated metastatic pancreatic adenocarcinoma (mPDAC): Phase (Ph) 2 final results.

Gemcitabine (Gem) and nab-paclitaxel (NP) ± nivolumab (nivo) ± CD40 agonistic monoclonal antibody APX005M (sotigalimab), in patients (Pts) with untreated metastatic pancreatic adenocarcinoma (mPDAC): Phase (Ph) 2 final results.

Abstract Video & Slides Poster

Authors

null

Mark H. O'Hara

University of Pennsylvania Abramson Cancer Center, Philadelphia, PA

Mark H. O'Hara , Eileen Mary O'Reilly , Robert A. Wolff , Zev A. Wainberg , Andrew H. Ko , Osama E. Rahma , George A. Fisher Jr., Jaclyn Paige Lyman , Christopher R. Cabanski , Joyson Joseph Karakunnel , Pier Federico Gherardini , Lacey J. Kitch , Samantha Bucktrout , Elizabeth Christopher , Rosemarie Mick , Richard Chen , Ovidiu C. Trifan , Lisa Salvador , Jill O'Donnell-Tormey , Robert H. Vonderheide

Organizations

University of Pennsylvania Abramson Cancer Center, Philadelphia, PA, Memorial Sloan Kettering Cancer Center, New York, NY, The University of Texas MD Anderson Cancer Center, Houston, TX, UCLA Medical Center, Los Angeles, CA, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Dana-Farber Cancer Institute, Boston, MA, Department of Medicine, Stanford University, Stanford, CA, Parker Institute for Cancer Immunotherapy, San Francisco, CA, University of Pennsylvania, Philadelphia, PA, Personalis, Inc., Menlo Park, CA, Apexigen, San Carlos, CA, Bristol Myers Squibb, Princeton, NJ, Cancer Research Institute, New York, NY, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA

Research Funding

Other Foundation
Parker Institute for Cancer Immunotherapy, Other Foundation, Pharmaceutical/Biotech Company

Background: Results from a ph1b trial evaluating gem/NP with CD40 agonistic monoclonal antibody APX005M ± nivo demonstrated promising clinical activity in pts with untreated mPDAC (O’Hara 2021). Herein, we report results from the follow-on, randomized (rand) ph2 trial evaluating gem/NP ± nivo ± APX005M. Methods: Pts with untreated mPDAC were rand to 1 of 3 open-label arms: gem/NP/nivo (A), gem/NP/APX005M (B), gem/NP/nivo/APX005M (C). All pts were treated with 1000 mg/m2 gem and 125 mg/m2 NP. Patients received 240 mg nivo in arms A and C and 0.3 mg/kg APX005M (RP2D) IV in arms B and C. Ph1b pts were included in ph2 analyses. 1° endpoint: 1-year OS rate of each arm, compared to a 35% historical OS rate for gem/NP (Von Hoff 2013). Key 2° endpoints: ORR, DCR, DOR, PFS and safety. Tumor and blood were collected for biomarker analysis. Planned enrollment of 35 pts/arm provided 81% power for testing the alternative of 58% OS rate vs 35%, using a 1-sided, 1-sample Z test with 5% type I error. Trial was not powered for cross-arm comparison. Results: 93 pts were rand in ph2 (N = 34, 30, 29 to A, B, C); when ph1b pts included, a total of 105 pts (34, 36, 35) were analyzed for efficacy and 108 pts (36, 37, 35) for safety. Min follow-up was 14 months (mos). Baseline characteristics were balanced across arms, inclusive of tumor burden, presence of liver metastases and stage at initial diagnosis (stage 1-3 vs 4). 1-year OS rate was 57% (1-sided p = 0.007 vs 35% historical rate, 95% lower CI bound = 41%) for A, 51% (p = 0.029, 95% bound = 36%) for B and 41% (p = 0.236, 95% bound = 27%) for C. Median OS and secondary endpoints are listed in Table. TRAE rates were similar across arms and to ph1b. 8 (7%) pts experienced an AE leading to tx discontinuation (6, 1, 1 in A, B, C), 40 (37%) pts experienced a serious TRAE (14, 15, 11 in A, B, C) and 2 pts died due to TRAEs; 1 each in B (acute hepatic failure) and C (intracranial hemorrhage). Conclusions: In this ongoing, seamless ph1b/2 trial of gem/NP ± nivo ± APX005M in pts with mPDAC, antitumor activity was observed in all arms. 1° endpoint of 1-year OS > 35% was met when combining gem/NP with either nivo or APX005M; however, not the combination. Safety was manageable; consistent with ph1b. Detailed multiomic immune and tumor biomarker analyses are underway to elucidate mechanisms of action and inform pt subsets that benefit most from these combinations. Clinical trial information: NCT03214250.

% (n) [95% CI]
A (n = 34)
B (n = 36)
C (n = 35)
ORR*
50 (17) [32–68]
33 (12) [19–51]
31 (11) [17–49]
ORR (confirmed)*
35 (12) [20–54]
33 (12) [19–51]
26 (9) [13–43]
DCR
74 (25) [56–87]
78 (28) [61–90]
69 (24) [51–83]
Median DOR, mos
4.8 [2.5–NE]
5.5 [3.7–7.6]
6.6 [1.9–NE]
Median PFS, mos
6.3 [5.2–8.8]
7.2 [5.3–9.2]
6.7 [4.1–9.8]
Median OS, mos
16.7 [9.8–20.4]
14.5 [7.2–20.1]
10.1 [7.9–13.2]
1-year OS, % [p]
57 [0.007]
51 [0.029]
41 [0.236]

*1 CR observed in A; NE = Not estimable.

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Pancreatic Cancer

Clinical Trial Registration Number

NCT03214250

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 4019)

DOI

10.1200/JCO.2021.39.15_suppl.4019

Abstract #

4019

Abstract Disclosures

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