Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as CD40 Agonistic Monoclonal Antibody, PYX-107, Sotigalimab
APX005M · 6 trials · 16 indications
The primary objective of this study is to determine the pathologic complete response (pCR) rate of the combined treatment modality.
The percentage of patients achieving a partial or complete response as measured by imaging assessments from study treatment
The pCR was defined as post-neoadjuvant pathologic tumour, node, metastasis (ypTNM) (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. * T0: No evidence of primary tumor. * N0: Cancer has not spread to nearby lymph nodes. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. Steroids use: Yes was defined as participants with any steroid (ATC2 class corticosteroids for systemic use) from within 30 days of the first dose of sotigalimab to up to 7 days after the first dose and participants not fulfilling previous requirements are defined as Steroids use: No. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
The pCR was defined as ypTNM (after chemoRT; after surgery) with T0, N0 stages. pCR rate was defined as the percentage of participants who achieved a pCR at surgery, as assessed by the Investigator. The subgroup of participants who had surgery before or at 16/17 weeks were defined as start of study treatment to surgery date from the surgical resection form, less than or equal to 17 weeks (119 days = 17 weeks \* 7 days) or participants who were scheduled to have surgery but had their procedure aborted due to progressive disease at the time of the procedure or immediately before and did not have surgery because of metastasis. The subgroup of participants who had surgery after Week 17 were defined as start of study treatment to surgery date from the surgical resection form, greater than 17 weeks. An exact Clopper-Pearson lower 95% confidence limit was used to test the null hypothesis that the pCR rate is ≤30%.
AEs and SAEs will be examined with (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03.
This 5-point scale ranges from full functioning (0) to dead (5)
All toxicities were graded according to the NCI-CTCAE version 4.03. DLT was defined as any of the following events attributed to APX005M and nivolumab combination: * Grade 4 hematologic toxicity lasting ≥ 7 days (except asymptomatic lymphopenia) * Grade 3 or 4 neutropenia with a single temperature of \>38.3◦ C (101◦ F) or a sustained temperature of ≥38◦ C (100.4◦ F) for more than one hour * Grade 4 thrombocytopenia or Grade ≥3 thrombocytopenia with signs or symptoms of bleeding or requiring platelet transfusion * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care * Any Grade ≥ 3 non-hematologic laboratory value if: medical intervention is required to treat the subject, abnormality leads to hospitalization, or abnormality persists for \>1 week * Failure to recover from a treatment-related AE to baseline or ≤ Grade 1 within 12 weeks of last dose of investigational product * Grade 5 toxicity.
Establish the MTD dose of APX005M combined with 360 mg of nivolumab for which for which \< 33% of DLT- evaluable participants experience a DLT. In Phase 1b, the RP2D was based on the overall safety and tolerability of the combination of APX005M and nivolumab by testing increasing doses up to 0.3 mg/kg APX005M + nivolumab.
ORR defined as the rate of patients who show as best overall response; either a complete response (CR) or a partial response (PR). The ORR can be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. using computed tomography (CT) scans/magnetic resonance imaging (MRI). Per RECIST v1.1, for target lesions and assessed by imaging: Complete Response, (CR), Disappearance of all target lesions and nontarget (NT) lesions; Partial Response (PR), \>30% decrease in the sum of the longest diameter of target lesions and no PD in NT lesions or new lesions; Objective Response Rate (ORR)=CR + PR.
The rate of DLTs will be assessed in approximately 56 subjects. DLTs will include Grade 4 neutropenia, anemia, thrombocytopenia, Grade 3or 4 nausea, cytokine release syndrome and other Grade 3 non-hematological toxicity
Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03
| Arm | Type | Description |
|---|---|---|
| APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX | EXPERIMENTAL | On Day 3 of Cycles 1-5 of each mFOLFOX treatment, participants will receive another dose of APX005M. The sequence of administration of APX005M in combination with mFOLFOX. In Cycle 6, participants will receive only mFOLFOX. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study. |
| Radiation Therapy 5Gy x 5 days, mFOLFOX | ACTIVE_COMPARATOR | Participants randomized to Arm 2 will receive short-course RT and mFOLFOX regimen, except that participants will not receive any of the study drug. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study. |
| Doxorubicin/APX005M | EXPERIMENTAL | Patients will be treated with doxorubicin and APX005M in 21 day cycles. All patients receive the same treatment (there is no "placebo" arm). After completing 8 cycles of study treatment, patients without evidence of disease progression or unacceptable toxicity may continue treatment with APX005M alone. Doxorubicin will not be continued beyond cycle 8 due to the risk for cardiac toxicity from cumulative dosing. |
| APX005M With Standard of Care Chemoradiation | EXPERIMENTAL | Participants will receive standard of care chemoradiation, consisting of: * External beam radiation in daily fractions (28 fractions) from Weeks 1-6, administered once per day up to 5 days/week. * Carboplatin (area under the carboplatin plasma concentration versus time curve = 2) and paclitaxel (50 mg/m\^2) chemotherapy intravenously (IV) over 1 hour, once weekly, from Weeks 1-5. The participants also will receive concurrent 0.3 mg/kg APX005M IV over 1 hour, once weekly, on Weeks 1, 2, 4, and 6 (2-3 days after chemoradiation). Surgical resection of the tumor will be planned from Week 10 up to approximately Week 17, as indicated in the protocol amendment under which each participant is enrolled. |
| Cohort 1 Advanced Solid Tumors | EXPERIMENTAL | Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles. |
| Cohort 2 Advanced Solid Tumors | EXPERIMENTAL | Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.03 mg/kg administered in 14 day cycles. |
| Cohort 3 Advanced Solid Tumors | EXPERIMENTAL | Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles. |
| Cohort 4 Advanced Solid Tumors | EXPERIMENTAL | Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.1 mg/kg administered in 14 day cycles. |
| Cohort 5 Advanced Solid Tumors | EXPERIMENTAL | Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles. |
| Cohort 6 Advanced Solid Tumors | EXPERIMENTAL | Nivolumab 240 mg plus Cabiralizumab 4mg/kg plus APX005M 0.3 mg/kg administered in 14 day cycles. |
| Cohort 7 Advanced Melanoma | EXPERIMENTAL | Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle. |
| Cohort 8 NSCLC | EXPERIMENTAL | Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle. |
| Cohort 9 RCC | EXPERIMENTAL | Patients will be treated at the estimated APX005M RP2D in combination with nivolumab 240 mg IV and cabiralizumab 4 mg/kg on day 1 of each 14-day cycle. |
| Phase 1b escalation 0.03 mg/kg | EXPERIMENTAL | Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.03 mg/kg and nivolumab 360 mg every 3 weeks |
| Phase 1b escalation 0.1 mg/kg | EXPERIMENTAL | Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.1 mg/kg and nivolumab 360 mg every 3 weeks |
| Phase 1b escalation 0.3 mg/kg | EXPERIMENTAL | Non-small cell lung cancer (NSCLC) or metastatic melanoma APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks |
| Phase 2 expansion Cohort 1 | EXPERIMENTAL | Immunotherapy naïve, metastatic or locally advanced NSCLC APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks |
| Phase 2 expansion Cohort 2 | EXPERIMENTAL | Metastatic melanoma progressing during treatment with anti-PD-1/PD-L1 therapy APX005M 0.3 mg/kg and nivolumab 360 mg every 3 weeks |
| Phase 2 expansion Cohort 3 | EXPERIMENTAL | Metastatic or locally advanced NSCLC progressing during treatment with anti-PD-1/PD-L1: * Group A: best response of progressive disease or with stable disease \< 16 weeks * Group B: tumor response or with stable disease ≥ 16 weeks |
| APX005M every 3 week | EXPERIMENTAL | Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death. |
| APX005M every 2 week | EXPERIMENTAL | Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death. |
| APX005M every 1 week | EXPERIMENTAL | Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death. |
| Name | Type | Description |
|---|---|---|
| APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days | DRUG | 1. APX005M 0.3mg/kg intravenously on day 3 of radiation and on day 3 of cycles 1-5 of mFOLFOX 2. Short course radiation therapy 5 Gy x 5 days 3. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle 4. Leucovorin 400mg/m2 IV Day 1 of each cycle 5. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle |
| mFOLFOX and Radiation Therapy 5Gy x 5 days | DRUG | 1. Short course radiation therapy 5 Gy x 5 days 2. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle 3. Leucovorin 400mg/m2 IV Day 1 of each cycle 4. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle |
| Doxorubicin | DRUG | Doxorubicin is an anthracycline antibiotic with antineoplastic activity 75 mg/m2 IV day 1 (21 day cycles) |
| APX005M | DRUG | APX005M is a CD40 agonistic monoclonal antibody 0.3 mg/kg IV day 1 (21 day cycles) |
| Radiation Therapy | RADIATION | Radiation therapy, total dose 5040cGy in 180cGy fractions |
| Paclitaxel | DRUG | Paclitaxel IV infusion |
| Carboplatin | DRUG | Carboplatin IV infusion |
| Surgical resection of tumor | PROCEDURE | Surgical removal of the tumor will occur between weeks 10-17 |
| Cabiralizumab | DRUG | Cabiralizumab is a humanized Immunoglobulin G (IgG) 4 monoclonal antibody directed against Colony stimulating factor 1 receptor (CSF1R). Cabiralizumab is administered by intravenous infusion. |
| Nivolumab | DRUG | Nivolumab is a humanized IgG4 monoclonal antibody directed against programmed cell death 1 (PD-1). Nivolumab is administered by intravenous infusion. |
Inclusion Criteria: 1. At least 18 years of age. Both men and women and members of all races and ethnic groups will be included. 2. Willing and able to provide written informed consent 3. Pathologic diagnosis of rectal adenocarcinoma 4. Stage III or Stage II with at least 1 of the following high-ri...
Top 20 of 40 competitors
APX005M is an investigational oncology drug developed by Pyxis Oncology, Inc. (ticker PYXS). It has been studied in clinical trials for several cancer types, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, esophageal and gastroesophageal junction cancers, locally advanced rectal adenocarcinoma, and soft tissue sarcoma. It remains in clinical development and is not approved for commercial use.
APX005M has been evaluated in clinical trials across multiple solid tumor types, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, esophageal and gastroesophageal junction cancers, locally advanced rectal adenocarcinoma, and soft tissue sarcoma. These studies examined its use both as a single agent and in combination with other therapies. It is investigational and not approved for any indication.
APX005M is developed by Pyxis Oncology, Inc., which trades under the ticker symbol PYXS. The company has sponsored clinical trials of the drug in multiple cancer indications, including rectal cancer, soft tissue sarcoma, melanoma, lung cancer, renal cell carcinoma, and esophageal cancer.
APX005M is in Phase 1 clinical development according to its overall development stage, though individual completed studies have been conducted at Phase 2. It is an investigational agent and has not been approved by the FDA for any indication. All listed trials of APX005M have been completed.
APX005M has been studied in completed trials including NCT04130854 (INNATE, neoadjuvant rectal cancer), NCT03719430 (with doxorubicin in advanced sarcoma), NCT03502330 (with nivolumab and cabiralizumab in advanced melanoma, NSCLC, or RCC), and NCT03165994 (with chemoradiation in esophageal and gastroesophageal junction cancers). All four trials are completed.
No. APX005M is an investigational drug and has not been approved by the FDA. It remains in clinical development, with its trials conducted in Phase 1 and Phase 2 settings across several cancer types. All of its listed clinical trials have been completed, and no regulatory approval has been granted for any indication.