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Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers

A Phase 1/2 Study of Galinpepimut-S in Combination With Pembrolizumab (MK 3475) in Patients With Selected Advanced Cancers

NCT03761914•Sellas Life Sciences Group

View on ClinicalTrials.gov

Summary

To evaluate the safety, tolerability, and anti-tumor activity of galinpepimut-S in combination with pembrolizumab in patients with selected advanced cancers.

Detailed Description

This is a Phase 1/2, open-label, non-comparative, multicenter, multi-arm (basket-type) study of galinpepimut-S (a multivalent WT1 analog peptide vaccine) in combination with the programmed death-1 (PD1) inhibitor pembrolizumab, in patients with metastatic colorectal cancer (mCRC), metastatic ovarian cancer (mOvC), advanced small-cell lung cancer (SCLC), triple-negative breast cancer (TNBC), and acute myeloid leukemia (AML). Additional details of tumors and prior therapies: mCRC treated with at least two prior lines, mOvC treated with at least one prior line, SCLC treated with one prior line, TNBC treated with at least one prior line, and AML unable to attain a morphological partial response after hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell transplant. The primary objectives of the study are to assess the safety, tolerability, and anti-tumor activity of galinpepimut-S in combination with pembrolizumab. The secondary and exploratory objectives include duration of response, overall survival, and progression-free survival. The study will enroll approximately 90 patients at up to 20 centers in the United States. The first two galinpepimut-S injections will initially be administered as monotherapy every three weeks (Week 0 and Week 3). Thereafter, galinpepimut-S will be co-administered with pembrolizumab every three weeks for four additional administrations (for the galinpepimut-S initial immunization induction phase series; weeks 6-15) to coincide with the per label pembrolizumab dosing frequency. After that, there will be one un-paired administration of pembrolizumab (week 18), and then galinpepimut-S will be resumed Q3W for six additional doses (early immune booster phase; weeks 21-36). At the end of this phase, there will be a 12-week interval where three unpaired administrations of pembrolizumab will occur (weeks 39-45), and then galinpepimut-S will be resumed on an every 12-week schedule for four additional doses (late immune booster phase; weeks 48-84). After 84 weeks, continuing non-progressed patients will be treated with pembrolizumab alone up until week 111. Pembrolizumab will be administered at a dose of 200 mg intravenously Q3W on Day 1 of each cycle (three week cycles) starting on Study Week 6 and continuing for up to two years thereafter (Study Week 111). Galinpepimut-S will be administered 30-60 minutes after the completion of IV infusion of pembrolizumab on Day 1 of each cycle during which the two drugs are being co-administered.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Yes

Inclusion Criteria

•Is willing and able to understand and provide signed informed consent for the study that fulfills IRB guidelines
•Male or female patients \>18 years of age on the day of signing informed consent
•Histologically or cytologically-confirmed advanced or metastatic solid tumors who have disease progression after treatment with available therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment in the context of the particular line of treatment or, specifically for AML, demonstrate as their best response after 4 cycles of HMA therapy the status of "partial response" per European LeukemiaNet (ELN) criteria and meet the additional specified requirements for the cohort of the study they will enroll into.
•All patients in the solid tumor arms will be tested for WT1 expression via IHC in their initial primary tumor OR recent biopsy of metastatic disease at the time of screening for study entry. Specifically for AML, patients will be tested for WT1 expression via IHC in their leukemic blasts either in the BM or PB. Assessment of WT1 expression positivity will be performed via central review prior to study entry.
•Patients may have received a specific maximum allowable number of prior lines of therapy for metastatic disease, as follows: CRC: 2 or 3 lines; OvC: 1 or 2 lines; SCLC: 1 line; TNBC: 1 line; and AML: 1 line (allo-SCT-eligible status not allowed)
•For solid tumor arms: patients must measurable disease based on RECIST v1.1 as determined by the local study team.
•For AML arm, eligibility is defined as:
•1. Prior frontline (1st line) with HMAs since initial AML diagnosis;
•2. Prior cytoreductive therapy with hydroxyurea or leukapheresis at the time of initial diagnosis, with subsequent immediate seamless transitioning to HMA therapy
•3. History of induction early failure after initial therapy with up to 2 cycles of standard chemotherapy ("7+3" or similar regimen), with subsequent immediate seamless transitioning to HMA therapy as long as patients have achieved PR as their best observable response after 4 cycles of HMA therapy; HMA therapy continues throughout the trial period.
+35 more criteria

Exclusion Criteria

•Presence of disease that is suitable for local or regional therapy administered with curative intent.
•Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
•* N.B.: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
•* N.B.: If the subject underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
•Has received prior radiotherapy within 2 weeks of the start of study treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
•Subject currently participates in a clinical trial with another investigational agent and is receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first study treatment.
•Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
•Has undergone prior allogeneic hematopoietic stem cell transplantation.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. Steroids taken as short-term therapy (≤ 7 days) for antiemesis are permissible.
+19 more criteria

Locations (12)

St. Joseph Heritage Healthcare

Santa Rosa, California, United States

Innovative Clinical Research Institute (ICRI)

Whittier, California, United States

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States