Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations

NCT05082025 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2020-1241NCI-2021-09936
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid tumors harboring alterations that activate the Phosphatidylinositol-3 kinase (PI3K) pathway.

Conditions

Endometrial Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  A DLT is defined as an intervention-related adverse event that impedes a patient from dosing a full cycle of copanlisib (3 doses), a delay of over 1 week in intitated study intervention occurring secondary to any study related adverse event, or death not clearly attrubuted to an underlying disease or alternate cause. Six out of the seven treated patients were evaluable for DLT. One patient was not evaluable for DLT due to not completing a full cycle of treatment within the first 28-days of treatment.

  Within the first cycle (28-days) of treatment.

• Number of Participants With Treatment-related Adverse Events

  Treatment-related adverse events that were deemed as possibly, probably, or definitely related to treatment, and were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. All treatment-related adverse events were captured from the time of signing consent through 30 days after the last dose of study drug or initation of a new anticancer therapy, whichever occurred first. The number of patients experiencing each treatment related adverse event (at least once) is reported.

  Through study completion, an average of 14 weeks.

Study Arms (2)

Part 1: Dose confirmation

EXPERIMENTAL

Up to 6 evaluable patients to confirm a single combination dose of copanlisib and fulvestrant

Drug: Copanlisib; Drug: fulvestrant

Part 2: Dose expansion:

EXPERIMENTAL

The dose expansion part will enroll in 3 indication-specific cohorts with 13 to 26 patients

Drug: Copanlisib; Drug: fulvestrant

Interventions

Copanlisib DRUG

Given by IV

Part 1: Dose confirmation; Part 2: Dose expansion:

fulvestrant DRUG

Given by IM

Part 1: Dose confirmation; Part 2: Dose expansion:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed ER+ and/or PR+ advanced or metastatic solid cancer including ovarian cancer (cohort 1), endometrial cancer (cohort 2), or breast cancer (cohort 3) (Figure 1). ER and/or PR positivity is defined as \>10% immunohistochemical staining of any intensity. Cohort 3 will be enriched to include at least 7 patients naive to any PI3Ki in Stage 1 and also in Stage 2.
• Presence of one or more PI3K and/or PTEN alterations in tumor tissue. Genetic alterations will include PIK3CA gain of function mutations, PIK3R1 loss of function mutations, PTEN loss of function mutations, and PTEN deletions.
• Measurable disease per the RECIST 1.1.
• The patient (or legally acceptable representative, if applicable) provides written informed consent for the study.
• Female or male ≥18 years of age on the day of informed consent signing.
• Patients have no available standard therapy known to prolong survival. For cohort 3 only, prior treatment with aPI3Ki or everolimus is not required and patients with or without prior PI3Ki or everolimus will be qualified for enrollment
• Adequate archived tumor tissue for the analysis for PI3K and PTEN alterations if available.
• Eastern Cooperative Oncology Group (ECOG) performance status of .2.
• Adequate organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Total bilirubin (TB) ≤1.5 × institutional upper limit of normal (ULN); Patients with known Gilbert's disease who have TB ≤3 × ULN may be enrolled)
• Aspartate transaminase (AST)/ alanine transaminase (ALT) ≤3 × ULN. If patient has liver metastases, AST and ALT ≤5.0 × ULN.
• Creatinine ≤1.5 x ULN

You may not qualify if:

• The patient has central nervous system (CNS) involvement. If the patient fulfills the following 3 criteria, she/he is eligible for the study:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases, and
• CNS tumor is radiologically stable for ≥ 28 days prior to study start, and
• The patient is not receiving steroids and enzyme-inducing antiepileptic medications for brain metastases.
• Patients with HER2 positive breast cancer.
• Patients must be ≥4 weeks or at least 5 half-lives beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents at the time of treatment initiation.
• \- NOTE: If the patient received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the study treatment.
• Prior treatment with fulvestrant or any PI3Ki for cohorts 1 and 2.
• Known hypersensitivity to copanlisib or fulvestrant, or to any of the excipients of copanlisib or fulvestrant.
• Concomitant use of strong cytochrome P450 (CYP)3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) or inhibitors (e.g., ritonavir, saquinavir, nelfinavir, boceprevir, telaprevir, ketoconazole, omeprazole). Use of strong inhibitors and/or inducers of CYP3A4 is not permitted from Day -14 of Cycle 1 until the start of the study intervention.
• The patient is currently receiving warfarin or other coumarin derived anticoagulants for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin, fondaparinux, or direct oral anticoagulants such as rivaroxaban or apixaban is allowed.
• Known additional malignancy that is progressing or requires active treatment.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient fs participation for the full duration of the study or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Known history of human immunodeficiency virus infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms

Interventions

copanlisib; Fulvestrant

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Timothy Yap
• Organization: The University of Texas MD Anderson Cancer Center

tyap@mdanderson.org

(713) 839-5458

Study Officials

• Timothy Yap, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: October 18, 2021
• Study Start: September 27, 2022
• Primary Completion: May 3, 2024
• Study Completion: December 12, 2025
• Last Updated: January 9, 2026
• Results First Posted: July 11, 2025

Record last verified: 2025-12

Locations

US (1)