Retifanlimab (INCMGA00012) and Telotristat Ethyl for the Treatment of Advanced Neuroendocrine Tumors and Carcinoid Syndrome

NCT04776876 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0083NCI-2021-00021
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies the effect of retifanlimab and telotristat ethyl in treating patients with neuroendocrine tumors that have spread to other places in the body (advanced) and carcinoid syndrome. Retifanlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Telotristat ethyl is a drug used to reduce side effects of carcinoid syndrome. Giving retifanlimab and telotristat ethyl may help to control neuroendocrine tumors in patients who also have carcinoid syndrome.

Conditions

Advanced Neuroendocrine Neoplasm; Carcinoid Syndrome

Outcome Measures

Primary Outcomes (1)

• Overall best response rate (partial response or complete response)

  Will estimate the best response rate and its 95% exact confidence interval using the Clopper and Pearson method.

  Up to 2 years

Secondary Outcomes (6)

• Objective response

  Up to 2 years

• Progression free survival

  Time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 2 years

• Duration of response

  Time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, assessed up to 2 years

• Disease control

  Up to 2 years

• Overall survival

  Time from enrollment to death from any cause, assessed up to 2 years

Study Arms (1)

Treatment (retifanlimab, telotristat ethyl)

EXPERIMENTAL

Patients receive retifanlimab IV over 30-60 minutes on day 1 and telotristat ethyl PO TID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Retifanlimab; Drug: Telotristat Ethyl

Interventions

Retifanlimab BIOLOGICAL

Given IV

Also known as: INCMGA 0012, INCMGA-0012, INCMGA00012, INCMGA0012, MGA 012, MGA-012, MGA012

Treatment (retifanlimab, telotristat ethyl)

Telotristat Ethyl DRUG

Given PO

Treatment (retifanlimab, telotristat ethyl)

Eligibility Criteria

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

You may qualify if:

• Grade 1, 2, or 3 (or described as low grade, intermediate grade, well differentiated, or moderately differentiated) neuroendocrine tumor, according to reviewing pathologist or documented interpretation of report by the investigator
• Progressive disease over the preceding 12 months
• Prior therapy with any number of anticancer therapies, but a somatostatin analogue (such as octreotide, lanreotide, or pasireotide) must be one of the prior therapies
• Carcinoid syndrome, as documented by the investigator
• Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrollment
• Signed informed consent form
• Age \>= 18 years
• Ability to comply with the study protocol, in the investigator's judgment
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count \>= 1,500/mm\^3 without granulocyte colony-stimulating factor support (obtained within 28 days prior to initiation of study treatment)
• Lymphocyte count \>= 500/mm\^3 (obtained within 28 days prior to initiation of study treatment)
• Platelet count \>= 100,000/mm\^3 without transfusion (obtained within 28 days prior to initiation of study treatment)
• White blood cell count \>= 2,500/mm\^3 (obtained within 28 days prior to initiation of study treatment)

You may not qualify if:

• Grade 3, poorly differentiated neuroendocrine carcinoma
• Large cell or small cell histology
• Treatment for the studied cancer within 28 days prior to initiation of study treatment
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is \> 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids for this purpose, and not have had radiation pneumonitis
• Toxicity of prior therapy that has not recovered to =\< grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support)
• Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (e.g., antihistamines and corticosteroids)
• Known allergy or hypersensitivity to any component of the INCMGA00012 formulation
• Known allergy or hypersensitivity to any component of the telotristat formulation
• Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent)
• Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted
• Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate
• Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication are permitted
• Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate
• Prior allogeneic stem cell or solid organ transplantation

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

MeSH Terms

Conditions

Serotonin Syndrome

Interventions

telotristat ethyl

Condition Hierarchy (Ancestors)

Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Study Officials

• Daniel M Halperin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: March 2, 2021
• Study Start: March 1, 2021
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: September 29, 2021

Record last verified: 2021-09