On November 8, 2024 Kineta, Inc. (OTC Pink: KANT), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported at the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) in Houston, TX an update on its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123, an anti-VISTA monoclonal antibody, as monotherapy and in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced solid tumors (Press release, Kineta, NOV 8, 2024, View Source;utm_medium=rss&utm_campaign=kineta-updates-kva12123-clinical-results-from-ongoing-phase-1-2-vista101-study-at-society-for-immunotherapy-of-cancer-2024 [SID1234648030]).

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KVA12123 cleared all six monotherapy dose levels and the second of four cohorts in combination with pembrolizumab. KVA12123 was well tolerated with no dose limiting toxicities (DLT) and a favorable safety profile at all dose levels in both arms of the study.

The poster presentation (SITC #625): "A phase 1/2 clinical trial of antiVISTA – KVA12123 alone and in combination with pembrolizumab in patients with advanced solid tumors" was presented by Dr. Jason Henry, M.D., Sarah Cannon Research Institute at HealthONE, Denver, CO, on Friday November 8, 2024 at 9 a.m. CST. The update included the following findings (with a data cutoff date of October 18, 2024):

Monotherapy Dose Escalation (3-1000 mg KVA12123 Q2W)

Of the 24 patients enrolled in the six monotherapy dose cohorts, 19 patients had at least one follow-up scan and 13 of these patients experienced stable disease (iRECIST).
Durable clinical outcomes have been observed in a number of monotherapy patients with one patient with non-small cell lung cancer that failed six prior lines of therapy, including checkpoint inhibitor (CPI) therapy, experiencing stable disease lasting 60 weeks.
Nine of 24 monotherapy patients had prior CPI exposure.
Combination Therapy Dose Escalation (30-100 mg KVA12123 Q2W, 400 mg pembrolizumab Q6W)

Nine patients have been enrolled in the two combination cohorts with at least one follow-up scan:
iCR and iPR responses have been observed and the combination has been well tolerated.
Confirmed Partial Response in one mucoepidermoid carcinoma patient with a 54% reduction in target lesions and a confirmed complete response (CR) in non-target lesions.
Stable disease in one renal cell carcinoma patient that had progressed on prior CPI therapy with a 24% reduction in target lesions.
Two remaining combination cohorts are expected to be fully enrolled by year-end.
Safety

No DLTs observed in any patient at any dose level in either study arm.
A very clean safety profile with few adverse events.
"We are pleased to present our progress on the VISTA-101 clinical trial at SITC (Free SITC Whitepaper) this year, with the initial clinical response data emerging from the study. We have observed promising clinical responses in this advanced cancer patient population. KVA12123 has the potential to be a new alternative for patients with hard-to-treat cancers," said Jason Henry, M.D. "The safety profile of KVA12123 to date has been remarkable in the monotherapy as well as in combination cohorts. Initial read-outs demonstrated that KVA12123 is not only safe but exhibits potential clinical benefit for some patients as either monotherapy or combination and may offer patients a novel approach to address immunosuppression in the tumor microenvironment and better manage solid tumor cancers," added Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta.

On July 8, 2024, Kineta announced that it had entered into an exclusivity and right of first offer agreement (the "Agreement") with TuHURA Biosciences, Inc. ("TuHURA"), a Phase 3 registration-stage immuno-oncology company developing novel technologies to overcome resistance to cancer immunotherapy. As part of the Agreement, Kineta received a $5 million nonrefundable payment from TuHURA in July 2024. In August 2024, Kineta announced that in collaboration with TuHURA, it reopened enrollment in the VISTA-101 clinical trial. Kineta and TuHURA continue to collaborate on the ongoing Phase 1 clinical program in patients with advanced solid tumor cancer. On October 2, 2024, Kineta announced that TuHURA was exercising its right to extend their exclusivity and right of first offer pursuant to the terms of the Agreement.

KVA12123 is a VISTA blocking immunotherapy in development as a twice weekly monoclonal antibody infusion drug being evaluated in a Phase 1/2 clinical trial for patients with advanced solid tumors. Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of cytokine release syndrome (CRS) in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 has been shown to de-risk the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer.

VISTA (V-domain Ig suppressor of T cell activation) is a negative immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA induces an efficient polyfunctional immune response to address immunosuppression and drives anti-tumor responses.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On November 8, 2024 Johnson & Johnson (NYSE:JNJ) reported the submission of regulatory applications to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking approval of a new indication for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in the U.S. and DARZALEX subcutaneous (SC) formulation in the European Union (EU) (Press release, Johnson & Johnson, NOV 8, 2024, View Source;johnson-submits-applications-in-the-us-and-eu-seeking-approval-of-darzalex-faspro–darzalex-as-subcutaneous-monotherapy-for-high-risk-smoldering-multiple-myeloma-302299496.html [SID1234648046]). The applications are supported by data from the ongoing Phase 3 AQUILA study (NCT03301220) of DARZALEX FASPRO as monotherapy for the treatment of adult patients with high-risk smoldering multiple myeloma.1

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Smoldering multiple myeloma is an early precursor of active multiple myeloma, where abnormal cells can be detected in the bone marrow, but patients are typically asymptomatic.2 Fifteen percent of all cases of newly diagnosed multiple myeloma are classified as smoldering multiple myeloma, and half of those diagnosed with high-risk disease will progress to active multiple myeloma within two years.3 Currently, smoldering multiple myeloma is not generally treated until active multiple myeloma develops. Instead, the standard approach is observation to track the disease for signs of biochemical progression and/or end organ damage, when treatment tends to be initiated.2 Recent evidence suggests that those at high-risk for progression to active multiple myeloma could benefit from earlier therapeutic intervention.4

"There remains an unmet need for early interventions and treatments that are both effective and well tolerated in people living with smoldering multiple myeloma at high-risk of progressing to active multiple myeloma," said Yusri Elsayed, M.D., M.H.Sc., Ph.D. Global Therapeutic Area Head, Oncology, Innovative Medicine, Johnson & Johnson. "DARZALEX has changed the standard of care in multiple myeloma, and with these submissions to the FDA and EMA, this therapy could become the first approved treatment for patients with high-risk smoldering multiple myeloma, potentially shifting the treatment paradigm."

The first data from the AQUILA study, evaluating the safety and efficacy of DARZALEX FASPRO compared to active monitoring in participants with high-risk smoldering multiple myeloma, will be presented at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego from December 7-10.4

About the AQUILA Study
AQUILA (NCT03301220) is a randomized, multicenter Phase 3 study investigating DARZALEX FASPRO versus active monitoring in patients (n=390) with high-risk smoldering multiple myeloma.1 The primary endpoint is progression free survival and secondary endpoints include time to progression, overall response rate and overall survival.1 Patients in the study were diagnosed with smoldering multiple myeloma in the last five years and were excluded if they had prior exposure to approved or investigational treatments for smoldering multiple myeloma or multiple myeloma.1

About Smoldering Multiple Myeloma
Smoldering multiple myeloma is an asymptomatic precursor state to multiple myeloma. Patients with smoldering multiple myeloma have higher levels of abnormal plasma cells in the bone marrow and an elevated monoclonal protein (M-protein) level in the blood, but they do not yet exhibit the symptoms commonly associated with active multiple myeloma, particularly end-organ damage. Fifteen percent of all cases of newly diagnosed multiple myeloma are classified as smoldering multiple myeloma, and half of those diagnosed with high-risk disease will progress to active multiple myeloma within two years.3

About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.6 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.7 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.8 People with multiple myeloma have a 5-year survival rate of 59.8 percent.8 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.9,10

About DARZALEX FASPRO and DARZALEX
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.11 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

DARZALEX (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.12

DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma.12 DARZALEX-based regimens have been used in the treatment of more than 518,000 patients worldwide and more than 68,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit www.DARZALEX.com.

DARZALEX FASPRO INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.

Local Reactions
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.

Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.

Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.

Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please click here to see the full Prescribing Information for DARZALEX FASPRO.

DARZALEX INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
CONTRAINDICATIONS
DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions
DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be lifethreatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia
DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusionrelated reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to see the full Prescribing Information for DARZALEX.

On November 7, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results and recent highlights for the third quarter ended September 30, 2024 (Press release, Cardiff Oncology, NOV 7, 2024, View Source [SID1234647923]).

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"This quarter has been exciting as our Phase 2 clinical trial in second-line KRAS-mutant mCRC was published in one of the most esteemed medical journals in the field of oncology, Journal of Clinical Oncology. Our findings demonstrated that onvansertib combined with FOLFIRI/bev was well-tolerated, and revealed a 7.7x greater clinical benefit in bev naïve patients compared to patients who were previously treated with bev," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We believe the results of our JCO publication validate our ongoing CRDF-004 trial evaluating onvansertib + chemo for the treatment of mCRC in the first-line setting, where all patients are bev naïve. Furthermore, we are pleased with the progress we have made in the trial as we leverage Pfizer’s resources and capabilities, and are grateful for the commitment from the patients and investigators at our trial sites across the U.S. As of today, the trial continues to generate patient data that will allow us to provide an initial data release by the end of the year. Overall, we are optimistic about onvansertib’s potential to become a meaningful treatment option for the 50,000 new patients diagnosed with RAS-mutated mCRC in the U.S. every year who have not had access to any new treatment options in several decades."

Upcoming expected milestones

•
First-line RAS-mutated metastatic colorectal cancer (mCRC) randomized initial data readout from the CRDF-004 trial expected by end of 2024

Company highlights for the quarter ended September 30, 2024 and subsequent weeks include:

•
Published clinical data of the combination of onvansertib with FOLFIRI and bev in second-line KRAS mutant mCRC in the peer-reviewed Journal of Clinical Oncology, the flagship publication of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)
•
Phase 2 clinical trial treating patients with KRAS-mutant mCRC (NCT03829410) demonstrated that onvansertib combined with FOLFIRI and bev was well-tolerated, and exhibited clinical activity in the second-line setting.
•
A post hoc analysis revealed a greater clinical benefit in bev naïve patients, who demonstrated an ORR of 77% and mPFS of 14.9 months compared to an ORR of 10% and mPFS of 6.6 months in those previously exposed to bev.

•
Published promising preclinical data demonstrating the combination of onvansertib and alpelisib in PIK3CA-mutated HR-positive breast cancer resistant to palbociclib and endocrine therapy in the peer-reviewed journal, Cancers
•
The combination of onvansertib and alpelisib synergistically inhibited cell viability, suppressed PI3K signaling, and induced G2/M arrest and apoptosis in PI3K-activated cell lines.
•
The combination demonstrated superior anti-tumor activity compared to the single agents in three PDX models.
•
Pharmacodynamic studies confirmed inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors.
•
The findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.
Third Quarter 2024 Financial Results

Liquidity, cash burn, and cash runway

As of September 30, 2024, Cardiff Oncology had approximately $57.7 million in cash, cash equivalents, and short-term investments.

Net cash used in operating activities for the third quarter of 2024 was approximately $10.5 million, an increase of approximately $2.5 million from $8.0 million for the same period in 2023.

Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into Q1 2026.

Operating results

Total operating expenses were approximately $12.8 million for the three months ended September 30, 2024, an increase of $1.8 million from $11.0 million for the same period in 2023. The increase in operating expenses was primarily due to clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib.

On November 7, 2024 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, reported the presentation of new clinical and translational data from its ongoing Phase 1/2 trial of NDI-101150, a novel, oral, potent and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, for the treatment of advanced solid tumors (Press release, Nimbus Therapeutics, NOV 7, 2024, View Source [SID1234647940]). Results will be highlighted in two poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, taking place November 6-10, 2024 in Houston, Texas.

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The Phase 1/2 multicenter, open-label trial (NCT05128487) is designed to assess NDI-101150 as a monotherapy (50-200 mg QD dose) and in combination with pembrolizumab (200 mg Q3W) in the treatment of adults with advanced solid tumors. The clinical results being presented at the SITC (Free SITC Whitepaper) Annual Meeting include updated safety data from 53 patients in the dose escalation cohorts (n=41 on monotherapy, n=12 on combination therapy) and additional data from 35 patients in the dose expansion cohorts as well as updated efficacy data from 17 response-evaluable patients with renal cell carcinoma (RCC) who received NDI-101150 monotherapy. Results, as of August 12, 2024, showed:

Safety Profile

NDI-101150 was generally well-tolerated with immune-related adverse events supporting the proposed mechanism of action of HPK1 inhibition, which results in immune activation.
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients exposed to NDI-101150 (n=88). The most common TRAEs were nausea, diarrhea, vomiting and fatigue.
Efficacy and Target Engagement

Treatment with NDI-101150 monotherapy resulted in objective responses in 18% (3/17) of response-evaluable RCC patients, including one complete response (CR) and two partial responses (PRs).
A clinical benefit rate (CR + PR + stable disease [SD] ≥6 months) of 29% (5/17) and a disease control rate of 65% (11/17) were observed in response-evaluable RCC patients treated with NDI-101150 monotherapy.
NDI-101150 effectively inhibited its target across multiple dose levels, providing strong pharmacodynamic evidence of the molecule’s activity in patients.
Supporting Mechanistic Evidence

Analysis of tumor biopsies showed a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment.
Comprehensive gene expression profiling demonstrated broad activation of immune-related pathways, including enhanced interferon response and T cell activation signals.
"These clinical results of NDI-101150 are highly encouraging, particularly in the context of renal cell carcinoma patients who have experienced disease progression on prior checkpoint inhibitors," said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Nimbus. "The objective responses and disease control rates seen thus far with NDI-101150 in heavily pretreated patients as well as the current safety profile support further evaluation of NDI-101150 in the clinic."

"The clinical and translational data package being presented at SITC (Free SITC Whitepaper) demonstrates both the therapeutic potential of NDI-101150 and the power of our computational drug discovery engine to design highly selective molecules against challenging targets like HPK1," said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. "The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own. Together with its safety profile and the immune activation signals we’ve observed, these data support NDI-101150’s potential as a novel oral non-checkpoint immunotherapy option for patients who need new treatment approaches beyond current checkpoint inhibitors."

The abstracts are available in the Journal for ImmunoTherapy of Cancer (JITC), the official journal of SITC (Free SITC Whitepaper), here and the details of the poster presentations are as follows:

Title: Ongoing Phase 1/2 Trial of the HPK1 Inhibitor NDI-101150 as Monotherapy and in Combination with Pembrolizumab: Clinical Safety Update and Renal Cell Carcinoma (RCC) Efficacy Analysis

Lead Author: David Sommerhalder, M.D., Director of Clinical Research, NEXT Oncology

Date: Saturday, November 9, 2024

Time: 9:00 a.m. – 8:30 p.m. CST

Category: Clinical Trials in Progress

Abstract Number: 682

Link to poster here.

Title: Tumor Immune Microenvironment Characterization from Pre- and Post-Dose Tumors Collected from a Phase 1/2 Study of NDI-101150, a Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor

Lead Author: Scott Daigle, Senior Director, Translational Medicine, Nimbus Therapeutics

Date: Friday, November 8, 2024

Time: 9:00 a.m. – 7:00 p.m. CST

Category: Biomarkers, Immune Monitoring and Novel Technologies

Abstract Number: 83

On November 7, 2024 Nektar Therapeutics (Nasdaq: NKTR) reported financial results for the third quarter ended September 30, 2024 (Press release, Nektar Therapeutics, NOV 7, 2024, View Source [SID1234647968]).

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Cash and investments in marketable securities on September 30, 2024 were $249.0 million as compared to $329.4 million at December 31, 2023. Nektar’s cash and marketable securities are expected to support strategic development activities and operations into the fourth quarter of 2026.

"We made excellent progress this quarter advancing our I&I pipeline, including the ongoing Phase 2b studies of rezpegaldesleukin in atopic dermatitis and alopecia areata," said Howard W. Robin, President and CEO of Nektar. "We see rapid enrollment in the 400-patient atopic dermatitis study for rezpegaldesleukin, and we remain on track for topline data in the first half of 2025. Our Phase 2 study in alopecia areata is also enrolling nicely with topline data expected in the second half of 2025."

"Beyond rezpegaldesleukin, we are focused on advancing our earlier stage TNFR2 antibody and bispecific programs, NKTR-0165 and NKTR-0166, with at least one of these slated to enter the clinic next year," continued Robin. "Next week, we are looking forward to presenting highly promising data at the 2024 ACR Convergence Meeting for our preclinical PEG-CSF program, NKTR-422. Finally, we recently published important data for our IL-15 agonist, NKTR-255, highlighting its potential as a validated mechanism in oncology."

Summary of Financial Results

Revenue in the third quarter of 2024 was $24.1 million compared to the same $24.1 million in the third quarter of 2023. Revenue for the first nine months of 2024 was $69.3 million compared to $66.2 million in the first nine months of 2023.

Total operating costs and expenses in the third quarter of 2024 were $58.5 million compared to $69.0 million in the third quarter of 2023. Total operating costs and expenses in the first nine months of 2024 were $188.8 million compared to $296.4 million in the first nine months of 2023. Operating costs and expenses for the first nine months of 2024 decreased primarily due to decreases in restructuring, impairment and costs of terminated programs and a one-time $76.5 million non-cash goodwill impairment recognized in the first quarter of 2023.

R&D expense in the third quarter of 2024 was $35.0 million compared to $24.1 million for the third quarter of 2023. For the first nine months of 2024, R&D expense was $92.2 million compared to $84.2 million in the first nine months of 2023. R&D expense increased for both the third quarter and the first nine months of 2024 primarily due to increases in development expenses for rezpegaldesleukin and NKTR-0165, partially offset by decreases in employee and related facilities costs, as well as development expenses for NKTR-255.

G&A expense was $19.0 million in the third quarter of 2024 compared to $21.1 million in the third quarter of 2023. G&A expense was $59.6 million for the first nine months of 2024 compared to $60.1 million in the first nine months of 2023. G&A expense decreased for both the third quarter and the first nine months of 2024 primarily due to decreases in employee costs, partially offset by the reduction of facilities costs allocated to research and development expenses.

Non-cash restructuring and impairment charges were less than $0.1 million in the third quarter of 2024 and $14.3 million in the first nine months of 2024. These non-cash charges are related to the declining San Francisco commercial real estate market and real estate lease obligations held by Nektar.

Net loss for the third quarter of 2024 was $37.1 million or $0.18 basic and diluted loss per share compared to a net loss of $45.8 million or $0.24 basic and diluted loss per share in the third quarter of 2023. Net loss in the first nine months of 2024 was $126.2 million or $0.62 basic and diluted loss per share compared to a net loss of $234.0 million or $1.23 basic and diluted loss per share in the first nine months of 2023. Excluding the $14.3 million in non-cash restructuring and real estate impairment charges, net loss, on a non-GAAP basis, for the first nine months of 2024 was $111.9 million, or $0.55 basic and diluted loss per share.

Third Quarter 2024 and Recent Business Highlights

● In September 2024, Nektar presented several posters for rezpegaldesleukin (REZPEG) at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. In addition to two trial-in-progress posters, new proteomic analyses were also presented, which showed that rezpegaldesleukin increased the protein levels of immune-regulating pathways and reduced specific serum proteins known to be elevated in patients with atopic dermatitis.

● In October 2024, Nektar and collaborators announced the publication of data from a Phase 1 trial evaluating NKTR-255 in combination with CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in Blood, an open-access journal of the American Society of Hematology (ASH) (Free ASH Whitepaper). The data show that eight out of nine patients (89%) achieved complete remission, all without detectable measurable residual disease (MRD).

● In October 2024, Nature Communications published results from Phase 1b studies of rezpegaldesleukin in two inflammatory skin diseases, demonstrating durable dose-dependent improvements in physician-assessed disease activity and patient-reported outcomes for both studies. Rezpegaldesleukin was evaluated in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). AD patients receiving high dose rezpegaldesleukin demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses were maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. Results validate the role of IL-2-induced Treg proliferation and activation in the AD treatment paradigm, and support the advancement of rezpegaldesleukin in the Phase 2b study in AD.

● In November, Nektar announced a definitive agreement with Ampersand Capital Partners to sell its commercial PEGylation manufacturing business in Huntsville, Alabama for $90 million in enterprise value, which is comprised of $70 million in cash and $20 million in equity ownership in the new portfolio company. The Huntsville-based facility will be spun out as a standalone Ampersand portfolio company and Ampersand has committed to invest additional growth equity capital into the new company. All of Nektar’s employees at the Huntsville facility will be offered employment at the new portfolio company, ensuring continuity in the high-quality manufacturing and PEGylation expertise that longstanding customers trust and rely on. Nektar and the new Ampersand portfolio company will also enter into manufacturing supply agreements to meet Nektar’s PEG reagent needs for rezpegaldesleukin and certain pipeline programs. The transaction will be subject to customary closing conditions and costs and is expected to close by December 2, 2024. Following the closing, Nektar will retain all rights to current and future royalty streams and milestones related to existing PEGylated product license agreements. Nektar will also be entitled to appoint a representative to the board of the new Ampersand portfolio company

● Enrollment remains on track for the two Phase 2b studies of REZPEG, one in patients with moderate-to-severe atopic dermatitis and one in patients with severe to very severe alopecia areata. Nektar expects topline data from these studies in the first half and in the second half of 2025, respectively.

Nektar also announced presentations at the following medical meetings:

2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting

Late-breaking Abstract (LBA) 1489: " REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): Preplanned Interim Safety and Efficacy Analysis", Lin, S.

Presentation Type: Poster
ePoster will be on display on the SITC (Free SITC Whitepaper) 2024 virtual meeting platform on Thursday, November 7, 2024, at 9:00 a.m. CST

2024 American College of Rheumatology (ACR) Convergence

Abstract 1866120: "A Novel Therapeutically Active CSF-1R Agonist Promotes Tissue Macrophages Inflammation Resolution and Induces Tissue Repair Pathways", Kivimae, S.
Presentation Type: Oral
Session: Abstracts: Cytokines & Cell Trafficking
Presentation Time: Monday, November 18 at 3:15 PM – 3:30 PM

2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting

Abstract 203576: "NKTR-255 Vs Placebo to Enhance Complete Responses and Durability Following CD19-Directed CAR-T Therapy in Patients with Relapsed/Refractory (R/R) Large B-cell Lymphoma (LBCL)", Ahmed, S.
Presentation Type: Poster
Session: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities
Presentation Time: Saturday, December 7 at 5:30 PM – 7:30 PM

Conference Call to Discuss Third Quarter 2024 Financial Results

Nektar management will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time on November 7, 2024.

This press release and live audio-only webcast of the conference call can be accessed through a link that is posted on the Home Page and Investors section of the Nektar website: View Source The web broadcast of the conference call will be available for replay through December 8, 2024.

To access the conference call, please pre-register at Nektar Earnings Call Registration. All registrants will receive dial-in information and a PIN allowing them to access the live call.