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Pemigatinib for Relapsed or Refractory Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement

The FDA approved pemigatinib for adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement. Efficacy was evaluated in FIGHT-203 (NCT03011372), a multicenter open-label, single-arm trial that included 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Eligible patients were either not candidates for or have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease-modifying therapy (e.g., chemotherapy). Pemigatinib was administered until disease progression, unacceptable toxicity, or patients were able to receive allo-HSCT.

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Selected demographics and baseline characteristics included the following: median age of 65 years (range, 39-78); 64 percent female; 68 percent White, 3.6 percent Black or African American, 11 percent Asian, and 3.6 percent American Indian/Alaska Native; and 88 percent ECOG performance status of 0 or 1.


Efficacy was established based on complete response (CR) rates per the response criteria relevant to the morphologic disease type. Of the 18 patients with chronic phase in the marrow with or without extramedullary disease (EMD), 14 achieved CR (78%; 95% CI: 52, 94). The median time to CR was 104 days (range, 44-435). The median duration was not reached (range: 1+ to 988+ days). Of the four patients with blast phase in the marrow with or without EMD, two achieved CR (duration: 1+ and 94 days). Of three patients with EMD only, one achieved a CR (duration: 64+ days). For all 28 patients, including three patients without evidence of morphologic disease, the complete cytogenetic response rate was 79 percent (22/28; 95% CI: 59, 92).


The most common (>=20%) adverse reactions occurring in patients were hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness.


The most common (>=10%) Grade 3 or 4 laboratory abnormalities were decreased phosphate, decreased lymphocytes, decreased leukocytes, decreased platelets, increased alanine aminotransferase, and decreased neutrophils. The recommended pemigatinib dose is 13.5 mg orally once daily on a continuous basis until disease progression or unacceptable toxicity.


Ibrutinib for Pediatric Patients With Chronic Graft-Versus-Host Disease

The FDA approved ibrutinib for pediatric patients >=1 year of age with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy. Formulations include capsules, tablets, and oral suspension.


Efficacy was evaluated in iMAGINE (NCT03790332), an open-label, multi-center, single-arm trial of ibrutinib for pediatric and young adult patients 1 year to less than 22 years old with moderate or severe cGVHD. The trial included 47 patients who required additional therapy after failure of one or more lines of systemic therapy. Patients were excluded if single organ genitourinary involvement was the only manifestation of cGVHD. The median age of patients was 13 years (range, 1-19). Selected demographics of the 47 patients were as follows: 70 percent male, 36 percent White, 9 percent Black or African American, 55 percent other or unreported.


The main efficacy outcome measure was overall response rate (ORR) through Week 25. ORR included complete response or partial responses, according to the 2014 NIH Consensus Development Project Response Criteria. ORR by Week 25 was 60 percent (95% CI: 44, 74). The median duration of response was 5.3 months (95% CI: 2.8, 8.8). The median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI: 4.6, not evaluable).


The most common (>=20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.


The recommended dosage of ibrutinib for patients 12 years of age and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2 orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.


First Antibody Candidate for DC-6001 Anti-CD93 Program

The FDA has cleared an investigational new drug (IND) application to advance the first monoclonal antibody candidate from the DC-6001 anti-CD93 development program into a Phase I study (NCT05496595). The study is designed to evaluate the safety and efficacy of DCBY02 in adult patients with a wide range of advanced cancers.


CD93 is a novel target that has been shown to play a critical role in the abnormal development of tumor vasculature, dysfunction that often creates a hypoxic tumor microenvironment and limits the efficacy of cancer therapies, including checkpoint inhibitors.


The DC-6001 program consists of two anti-CD93 monoclonal antibodies, each of which has demonstrated distinct in vitro and in vivo properties and the ability to block different epitopes of CD93 in pre-clinical development. The Phase I program consists of two parts: a dose-escalation phase (Part 1) to determine a recommended Phase II dose (RP2D), followed by a dose-expansion phase (Part 2) at the RP2D. Both parts aim to include adult patients with a variety of locally advanced or metastatic solid tumors.


"It has been known for 2 decades that inadequate tumor vascularization deteriorates the outcome of chemotherapeutic agents due to hypoxia. Our research has shown that normalization of malignant tumor vasculature is required to turn the tumor microenvironment from immunosuppressive to immunostimulatory," noted Lieping Chen, MD, PhD, Professor of Immunobiology at Yale University. "We believe that targeting the CD93 pathway holds the potential to improve hypoxia and enhance the efficacy of other anti-cancer agents. The approval of this IND marks an important step forward in our ongoing research into pioneering ways to harness the immune system and treat a number of difficult-to-treat cancers."