Reference Detail

Ref Type

Abstract

PMID

Authors

T.A. Yap S.A. Piha-Paul D. Karp E.E. Dumbrava D.S. Hong S. Fu V. Subbiah A.M. Tsimberidou J. Rodon J. Rhudy C. Valladolid Y. Yuan B. Jana P. Spiliopoulou L. Randall A. Poklepovic K. Sehgal G.I. Shapiro R. Said F. Meric-Bernstam

Title

701P NCI10221: Phase II multicenter biomarker driven combination trial of copanlisib and nivolumab in patients with molecularly-selected advanced solid tumors (BaCoN)

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Supplement 2	October 2023	S487-S488	Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(23)02724-2/fulltext

Abstract Text

Background Preclinical data showed antitumor efficacy with PI3K and PD-1 combined blockade. We hypothesized that efficacy will be enriched in tumors with PIK3CA hotspot and PTEN mutations vs those without. This provided rationale for this 3-arm trial of copanlisib (pan-PI3K inhibitor) and nivolumab (PD-1 inhibitor) in patients (pts) with: (1) activating PIK3CA hotspot mutations, (2) inactivating PTEN mutations or (3) wildtype (WT) for PIK3CA/PTEN mutations (NCT04317105). Methods Copanlisib was started as monotherapy in cycle 1 at 60 mg IV D1, 8, 15, before nivolumab was added from cycle 2 at 480 mg IV every 28 days. Fresh tumor biopsies and ctDNA were mandated in all pts at baseline, copanlisib monotherapy, on combo and at progression. Prior PD-1/L1 or PI3K inhibitors (PD-1/L1i or PI3Ki) were allowed. Objectives were safety, antitumor activity and analyses of sequential tumors (WES; RNA-Seq; RPPA) and ctDNA. Results 50 pts (M:F 17:33; ECOG PS 0:1 18:32; mean age 58 years (27-79) with ovarian (n=12), breast (n=10), HNSCC (n=4), bile duct (n=3), NSCLC (n=3), prostate (n=3), colon (n=3), gallbladder (n=2), leiomyosarcoma (n=2), salivary gland (2), bladder, cervical, endometrial, liposarcoma, sarcoma, skin (n=1) cancers enrolled. Pts with PIK3CA hotspot (n=16), PTEN (n=18), and WT (n=16) tumors enrolled. 31/50 pts had ≥3 lines of prior therapy; 23 (46%)/50 pts had prior PD-1/L1i and 3 (6%)/50 prior mTOR inhibitors. Common toxicities: G1/2 nausea (35%), rash (24%), diarrhea (24%), mucositis (20%), anemia (20%), fatigue (18%), hyperglycemia (18%); ≥ G3 transient hypertension (24%). RECISTv1.1 CR/PR in PIK3CA and PTEN cohorts were achieved in 4 (27%)/15 (1 cPR; 3 uCR/PR) pts and 3 (20%)/15 (3 cPR) pts, vs 0/15 (0%) pts in WT cohort. Responses were deep (up to -100%) and durable (up to 15+ months). Clinical benefit rate (SD>4 months/CR/PR) was 29% across cohorts; 40% in PIK3CA hotspot cohort, 33% in PTEN cohort and 13% in WT cohort. Conclusions The combination of copanlisib and nivolumab is well tolerated with antitumor activity in pts with PIK3CA hotspot and PTEN mutations including PD-1/L1i-exposed pts. Translational analyses are ongoing. Clinical trial identification NCT04317105.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PTEN inact mut	Advanced Solid Tumor	predicted - sensitive	Copanlisib + Nivolumab	Phase II	Actionable	In a Phase II trial (BaCoN), treatment with the combination of Aliqopa (copanlisib) and Opdivo (nivolumab) was well tolerated in patients with advanced solid tumors harboring an inactivating mutation in PTEN, and resulted in a complete response/partial response (CR/PR) in 20% (3/15, 3 cPR) and a clinical benefit rate (CR or PR or stable disease > 4 months) of 33% (Ann Oncol 34 (2023): S487-S488; NCT04317105).	detail...
PIK3CA act mut	Advanced Solid Tumor	predicted - sensitive	Copanlisib + Nivolumab	Phase II	Actionable	In a Phase II trial (BaCoN), treatment with the combination of Aliqopa (copanlisib) and Opdivo (nivolumab) was well tolerated in patients with advanced solid tumors harboring an activating mutation in PIK3CA, and resulted in a complete response/partial response (CR/PR) in 27% (4/15, 1 cPR, 3 uCR/PR) and a clinical benefit rate (CR or PR or stable disease > 4 months) of 40% (Ann Oncol 34 (2023): S487-S488; NCT04317105).	detail...