Part A- Recurrent and metastatic non-small cell lung cancer (NSCLC), pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma Part B- Recurrent or metastatic immune checkpoint refractory NSCLC Part C- Metastatic pancreatic cancer MedDRA version: 21.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classifica
Conditions
Interventions
Product Code: CM24
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CM24
Other descriptive name: Humanised IgG4k monoclonal antibody against Carcinoembryonic antigen-related cell adhesi
Sponsors
Famewave Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A 1. Previously treated subjects with recurrent and metastatic NSCLC, pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma with documented progression/intolerance following at least one previous therapy (and not more than 2 previous regimens). 2. Adequate safety lab results at Screening and at Baseline (Day 1) for those tests that require repeating at Baseline, including the following: a. Albumin =3 g/dL; b. Bilirubin =1.5 times the upper limit of normal (ULN) or 40 mL/minute based on the Cockcroft-Gault equation [creatinine clearance in mL/min = (140 – age in years) x body weight (kg)/72 x serum creatinine (mg/dL); multiplied by 0.85 for women]; e. White blood cell (WBC) count =2000/uL; neutrophils =1500/uL; hemoglobin =9 g/dL; platelets =100x103/uL. 3. Brain metastases should be stable following radiosurgery with at least 4 weeks since the end of definitive therapy (i.e., radiotherapy) and without need for steroid therapy as evidenced by imaging performed after completion of any CNS directed therapy demonstrating radiographic stability of CNS lesions. 4. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy. 5. Age =18 years at the time of signing ICF; Part B 1. Subjects with histologically confirmed metastatic or locally advanced non-small cell lung cancer (NSCLC) with documented progression following anti-PD-1/PD-L1 containing therapy; Subjects must have confirmation of progression of disease that is consistent with iCPD during or within 3 months of prior anti-PD1/PDL1 with either two radiographic scans showing disease progression or documented clinical progression (e.g., worsening of symptoms). 2. Subjects could have had a maximum of 1 prior treatment regimen. 3. Adequate safety lab results at Screening and at Baseline (Day 1) for those tests that require repeating at Baseline, including the following: a. Albumin =3 g/dL; b. Bilirubin =1.5 times the upper limit of normal (ULN) or 40 mL/minute based on the Cockcroft-Gault equation [creatinine clearance in mL/min = (140 – age in years) x body weight (kg)/72 x serum creatinine (mg/dL); multiplied by 0.85 for women]; e. White blood cell (WBC) count =2000/uL; neutrophils =1500/uL; hemoglobin =9 g/dL; platelets =100x103/uL. 4. Brain metastases should be stable following radiosurgery with at least 4 weeks since the end of definitive therapy (i.e., radiotherapy) and without need for steroid therapy as evidenced by imaging performed after completion of any CNS directed therapy demonstrating radiographic stability of CNS lesions. 5. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy. Part C 1. Subjects with histologically confirmed metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded. 2. Subjects with a maximum of 1 prior treatment regimen for metastatic disease excluding nab-paclitaxel containing regimens and up to 8 weeks fro
Exclusion criteria
Exclusion criteria: Part A 1. History of weight loss >10% over the 2 months prior to Screening. 2. Received more than two prior systemic regimens for the metastatic disease. 3. Unresolved AEs > Grade 1 from prior anticancer therapy. Exempted are effects that are often non-reversible or require a prolonged time for reversal (e.g., alopecia, hypothyroidism, neuropathy). 4. Concurrent malignancy requiring treatment. Participants with a previously treated malignancy are eligible if treatment was completed at least 2 years before study start and the patient has no evidence of disease. Participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment or with a history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible. 5. Active, untreated central nervous system (CNS) metastases. 6. Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity of = Grade 3, treatment of their toxicity with systemic corticosteroids, or any hypersensitivity to PD-1/PDL-1 targeting agents or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways. 7. Severely immunocompromised as defined by white blood cell (WBC) count 10% over the 2 months prior to Screening; 2. Received more than 1 prior systemic regimens for the advanced/recurrent and/or metastatic disease; 3. Unresolved AEs > Grade 1 from prior anticancer therapy. Exempted are effects that are often non-reversible or require a prolonged time for reversal (e.g., alopecia, hypothyroidism, neuropathy). 4. Concurrent malignancy requiring treatment. Participants with a previously treated malignancy are eligible if treatment was completed at least 2 years before study start and the patient has no evidence of disease. Participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment or with a history of prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have undergone definitive treatment at any time are also eligible. 5. Active and/or untreated central nervous system (CNS) metastases including leptomeningeal metastases; 6. Severely immunocompromised as defined by white blood cell (WBC) count <2000/mm3 and/or CD4+ lymphocyte count =200/mm3. 7. History of allergy or hypersensitivity to any of the study treatment components; subjects previously treated with an anti PD-1/PD-L1 targeting agent with history of immune-mediated toxicity of = Grade 3 treatment of their toxicity with systemic corticosteroids, or any hypersensitivity to PD-1/PD-L1 targeting agents or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 8. Major surgery within 4 weeks of study administration; 9. Participants who have received a l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A • To assess the safety, tolerability and the maximum tolerated dose (MTD) of CM24 in combination with 480mg nivolumab in adults with selected recurrent or metastatic solid tumors. • Determine the recommended Phase 2 dose level (RP2D) of CM24 in combination with nivolumab Part B To assess the efficacy of the recommended phase 2 dose (RP2D) of CM24 in combination with nivolumab in adults with immune-checkpoint refractory recurrent or metastatic NSCLC based on Objective Response Rate (ORR). Part C To assess the efficacy of CM24 in combination with nivolumab and nabpaclitaxel in adults with metastatic pancreatic cancer based on Objective Response Rate.;Secondary Objective: Part A 1. Characterize the pharmacokinetic profile of CM24 in combination with nivolumab. 2. Characterize the immunogenicity of CM24 in combination with nivolumab. 3. To assess the preliminary efficacy of different dose levels of CM24 in combination with nivolumab: o Objective response rate (ORR) o Disease control rate (DCR) o Median duration of response (DoR) o Median time to response o 6, 12 and 18 month and median progression free survival (PFS) o 6, 12, 18 months and median overall survival (OS) Part B 1. To further assess the efficacy of the RP2D of CM24 in combination with nivolumab based on, but not limited to: o Disease control rate (DCR) o Median duration of response (DoR) o Median time to response Part C 1. To further assess the efficacy of CM24 in combination with nivolumab and nab-paclitaxel based on, but not limited to: o Disease control rate (DCR);Primary end point(s): Part A Safety and tolerability Parts B and C Objective response rate (ORR) based on RECIST Version 1.1;Timepoint(s) of evaluation of this end point: Part A Following study drug administration on Day 1 and within 100 days of the last dose of CM24, nivolumab or nab-paclitaxel (whichever is last). Parts B and C Tumor imaging (either CT, PET/CT or MRI) will be performed at Screening, within 1 week | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A 1. Serum PK parameters for CM24 following administration of CM24 in combination with nivolumab on Day 1 and Day 15 will be calculated if measurable serum levels are observed, and will include Cmax, Tmax, AUC0-T, AUC0-8, t1/2, CL, and Vd. 2. Serum ADA parameters for CM24 of on Day 1 of Cycle 1, 2 and 5 and the Study Follow up Visits; the proportion of subjects developing ADA will be determined. Positive ADA samples will be characterized for their ability to neutralize binding of CM24 to CEACAM1. 3. Efficacy endpoints at different dose levels of CM24 in combination with nivolumab will include the following analyses (per dose level): o Objective response rate (ORR) o Disease control rate (DCR) o Median duration of response (DoR) o Median time to response (TTR) o 6, 12 and 18 month and median progression free survival (PFS) o 6, 12, 18 months and median overall survival (OS) Part B 1. Efficacy based on disease control rate (DCR), duration of response (DoR) and time to response (TTR), median progression free survival (PFS) as well as 6, 12 and 18 month PFS and 6, 12, 18 month and median overall survival (OS). ORR, DCR, DoR, TTR and PFS endpoints will be determined based on CR, PR, SD and PD as defined by RECIST Version 1.1. Exploratory analyses of efficacy will be done based on iCR, iPR, iSD and iCPD as defined by iRECIST. 2. Safety based on the same primary and secondary assessments described for the dose escalation phase, minus the MTD determination.;Timepoint(s) of evaluation of this end point: Part A 1. Cycle 1 Day 1, predose, within 5min postdose, 1.5 & 3h postdose, Day 2, 4, 8 & 15 predose, Day 15 within 5 min & 1.5h post dose; Day 1 on Cycle 2, 3, 5, 6, 7, 9, 13, 17, 21, 24 & on study follow up visits 30, 60 & 100 days post last treatment. 2. Day 1 of Cycles 1, 2, 3, 5, 9, 13, 17, 21, 24. 3. Screening, within 1 week following completion of Cycle 2 & approx. every 8 weeks thereafter. Part B 1. Screening, within 1 week following the | — |
Countries
Israel, Spain, United States
Contacts
Public ContactMichael Schickler
Famewave Ltd.
Outcome results
None listed